title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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N-acyl-homoserine lactones-producing bacteria protect plants against plant and human pathogens. | The implementation of beneficial microorganisms for plant protection has a long history. Many rhizobia bacteria are able to influence the immune system of host plants by inducing resistance towards pathogenic microorganisms. In this report, we present a translational approach in which we demonstrate the resistance-inducing effect of Ensifer meliloti (Sinorhizobium meliloti) on crop plants that have a significant impact on the worldwide economy and on human nutrition. Ensifer meliloti is usually associated with root nodulation in legumes and nitrogen fixation. Here, we suggest that the ability of S. meliloti to induce resistance depends on the production of the quorum-sensing molecule, oxo-C14-HSL. The capacity to enhanced resistance provides a possibility to the use these beneficial bacteria in agriculture. Using the Arabidopsis-Salmonella model, we also demonstrate that the application of N-acyl-homoserine lactones-producing bacteria could be a successful strategy to prevent plant-originated infections with human pathogens. | 25,234,390 | [
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Do we need primer for orthodontic bonding? A randomized controlled trial. | To evaluate the clinical performance of APC™II Victory Series™ (3M Unitek) brackets in direct orthodontic bonding with and without the use of primer. A single-operator, two-centre prospective, non-inferiority randomized controlled clinical trial. The Orthodontic departments at the Leeds Dental Institute and St Luke's Hospital, Bradford, UK. Ethical approval was granted by Leeds (East) Research Ethics Committee on 18th of December 2009 (Reference 09/H1306/102). The protocol was not published prior to trial commencement. Ninety-two patients requiring orthodontic treatment with fixed appliances were randomly allocated to the control (bonded with primer) or test groups (bonded without primer). Patients were randomly allocated to either the control or experimental group. This was performed by preparing opaque numbered sealed envelopes in advance using a random numbers table generated by a computer by an independent third party . Once the envelopes were opened, blinding of the operator and the patient was no longer possible due to the nature of the intervention. Patients were approached for inclusion in the trial if they qualified for NHS orthodontic treatment requiring fixed appliances and had no previous orthodontic treatment. Number of bracket failures, time to bond-up appliances, and the adhesive remnant index (ARI) when bracket failure occurred, over a 12-month period Failure rate with primer was 11.1 per cent and without primer was 15.8 per cent. Bonding without primer was shown statistically to be non-inferior to bonding with primer odds ratio 0.95-2.25 (P = 0.08). Mean difference in bond-up time per bracket was 0.068 minutes (4 seconds), which was not statistically significant (P = 0.402). There was a statistically significant difference in the Adhesive Remnant Index - ARI 0 with primer 49.4 per cent, no primer 76.5 per cent, (P < 0.0001). As the study was only performed by one operator, the results can therefore only be truly be applied to their practice. Also this study was powered to ascertain if there was no difference between the 2 groups up to 5%, however orthodontists may consider a change in the bracket failure rate of 2% to be clinically significant. When bonding with APC™II Victory Series™ brackets without primer was shown statistically to be non-inferior to bonding with primer (P =0.08). There was no significant difference in bond-up times. Bond failure was more likely to happen at the composite-enamel interface when bonded without a primer. No conflict of interest for all authors. No funding sources were used. Study was not registered on external databases. | 25,234,405 | [
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Tunable thermodynamic stability of Au-CuPt core-shell trimetallic nanoparticles by controlling the alloy composition: insights from atomistic simulations. | A microscopic understanding of the thermal stability of metallic core-shell nanoparticles is of importance for their synthesis and ultimately application in catalysis. In this article, molecular dynamics simulations have been employed to investigate the thermodynamic evolution of Au-CuPt core-shell trimetallic nanoparticles with various Cu/Pt ratios during heating processes. Our results show that the thermodynamic stability of these nanoparticles is remarkably enhanced upon rising Pt compositions in the CuPt shell. The melting of all the nanoparticles initiates at surface and gradually spreads into the core. Due to the lattice mismatch among Au, Cu and Pt, stacking faults have been observed in the shell and their numbers are associated with the Cu/Pt ratios. With the increasing temperature, they have reduced continuously for the Cu-dominated shell while more stacking faults have been produced for the Pt-dominated shell because of the significantly different thermal expansion coefficients of the three metals. Beyond the overall melting, all nanoparticles transform into a trimetallic mixing alloy coated by an Au-dominated surface. This work provides a fundamental perspective on the thermodynamic behaviors of trimetallic, even multimetallic, nanoparticles at the atomistic level, indicating that controlling the alloy composition is an effective strategy to realize tunable thermal stability of metallic nanocatalysts. | 25,234,428 | [
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Neutral nuclear variation in Baboons (genus Papio) provides insights into their evolutionary and demographic histories. | Baboons (genus Papio) are distributed over most of sub-Saharan Africa and in the southern portion of the Arabian Peninsula. Six distinct morphotypes, with clearly defined geographic distributions, are recognized (the olive, chacma, yellow, Guinea, Kinda, and hamadryas baboons). The evolutionary relationships among baboon forms have long been a controversial issue. Phylogenetic analyses based on mitochondrial DNA sequences revealed that the modern baboon morphotypes are mitochondrially paraphyletic or polyphyletic. The discordance between mitochondrial lineages and morphology is indicative of extensive introgressive hybridization between ancestral baboon populations. To gain insights into the evolutionary relationships among morphotypes and their demographic history, we performed an analysis of nuclear variation in baboons. We sequenced 13 noncoding, putatively neutral, nuclear regions, and scored the presence/absence of 18 polymorphic transposable elements in a sample of 45 baboons belonging to five of the six recognized baboon forms. We found that the chacma baboon is the sister-taxon to all other baboons and the yellow baboon is the sister-taxon to an unresolved northern clade containing the olive, Guinea, and hamadryas baboons. We estimated that the diversification of baboons occurred entirely in the Pleistocene, the earliest split dating ∼1.5 million years ago, and that baboons have experienced relatively large and constant effective population sizes for most of their evolutionary history (∼30,000 to 95,000 individuals). | 25,234,435 | [
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A modified Mediterranean diet score is associated with a lower risk of incident metabolic syndrome over 25 years among young adults: the CARDIA (Coronary Artery Risk Development in Young Adults) study. | The Mediterranean diet has been reported to be inversely associated with incident metabolic syndrome (MetSyn) among older adults; however, this association has not been studied in young African American and white adults. The objective of the present study was to evaluate the association of a modified Mediterranean diet (mMedDiet) score with the 25-year incidence of the MetSyn in 4713 African American and white adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. A diet history questionnaire was used to assess dietary intake at baseline, year 7 and year 20 and a mMedDiet score was created. Cardiovascular risk factors were measured at multiple examinations over 25 years. The MetSyn was defined according to the National Cholesterol Education Program Adult Treatment Panel III (ATP III) criteria. Cox proportional-hazards regression analysis was use to evaluate associations for incident MetSyn across the mMedDiet score categories adjusting for demographic characteristics, lifestyle factors and BMI. Higher mMedDiet scores represented adherence to a dietary pattern rich in fruit, vegetables, whole grains, nuts and fish, but poor in red and processed meat and snack foods. The incidence of MetSyn components (abdominal obesity, elevated TAG concentrations and low HDL-cholesterol concentrations) was lower in those with higher mMedDiet scores than in those with lower scores. Furthermore, the incidence of the MetSyn was lower across the five mMedDiet score categories; the hazard ratios and 95 % CI from category 1 to category 5 were 1·0; 0·94 (0·76, 1·15); 0·84 (0·68, 1·04); 0·73 (0·58, 0·92); and 0·72 (0·54, 0·96), respectively (P trend= 0·005). These findings suggest that the risk of developing the MetSyn is lower when consuming a diet rich in fruit, vegetables, whole grains, nuts and fish. | 25,234,439 | [
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Central blockade of nitric oxide transmission impairs exercise-induced neuronal activation in the PVN and reduces physical performance. | The blockade of central nitric oxide (NO) signaling modifies the thermoregulatory and metabolic adjustments that occur during exercise, thereby impairing physical performance. However, the brain areas involved in this response remain unknown. Nitrergic neurons are present in the hypothalamic areas that are activated during exercise and participate in autonomic and neuroendocrine responses, such as, the hypothalamic paraventricular nucleus (PVN) and the supraoptic nucleus (SON). To investigate whether brain NO signaling affects thermoregulation during exercise through the activation of hypothalamic neurons, rats underwent acute submaximal treadmill exercise (18 mmin(-1), 5% inclination) until fatigue received an intracerebroventricular injection of 1.43 μmol Nω-nitro-l-arginine metil ester (L-NAME), a nitric oxide synthase inhibitor, or saline (SAL). Skin tail temperature (Tsk) and internal body temperature (Ti) were continuously recorded and c-Fos expression was determined in the PVN and the SON. L-NAME treatment reduced physical performance by 48%, which was positively correlated with tail vasodilation capacity, which was reduced by 28%, and negatively correlated with heat storage rate (HSR), which was increased by 38%. Physical exercise until fatigue increased the number of c-Fos-immunoreactive (ir) neurons in the PVN and the SON. L-NAME-treatment significantly reduced the exercise-induced c-Fos expression in the PVN, whereas it had no effect in the SON. Interestingly, the number of c-Fos-ir neurons in the PVN was closely correlated with physical performance and inversely associated with HSR. Thus, the inhibition of central NO attenuates neuronal activation induced by exercise in the PVN, impairs the autonomic regulation of heat dissipation, and anticipates the fatigue. Brain NO seems to play a role in exercise performance through the regulation of neuronal activation in the PVN, but not in the SON, although the SON neurons are also activated by running exercise. Moreover, this role in performance mediated by neuronal activation in the PVN can be related with the improvement of thermoregulatory adjustments that occur during exercise. | 25,234,442 | [
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Efficient In vitro labeling rabbit bone marrow-derived mesenchymal stem cells with SPIO and differentiating into neural-like cells. | Mesenchymal stem cells (MSCs) can differentiate into neural cells to treat nervous system diseases. Magnetic resonance is an ideal means for cell tracking through labeling cells with superparamagnetic iron oxide (SPIO). However, no studies have described the neural differentiation ability of SPIO-labeled MSCs, which is the foundation for cell therapy and cell tracking in vivo. Our results showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) labeled in vitro with SPIO can be induced into neural-like cells without affecting the viability and labeling efficiency. The cellular uptake of SPIO was maintained after labeled BM-MSCs differentiated into neural-like cells, which were the basis for transplanted cells that can be dynamically and non-invasively tracked in vivo by MRI. Moreover, the SPIO-labeled induced neural-like cells showed neural cell morphology and expressed related markers such as NSE, MAP-2. Furthermore, whole-cell patch clamp recording demonstrated that these neural-like cells exhibited electrophysiological properties of neurons. More importantly, there was no significant difference in the cellular viability and [Ca(2+)]i between the induced labeled and unlabeled neural-like cells. In this study, we show for the first time that SPIO-labeled MSCs retained their differentiation capacity and could differentiate into neural-like cells with high cell viability and a good cellular state in vitro. | 25,234,466 | [
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Cognitive set shifting deficits and their relationship to repetitive behaviors in autism spectrum disorder. | The neurocognitive impairments associated with restricted and repetitive behaviors (RRBs) in autism spectrum disorder (ASD) are not yet clear. Prior studies indicate that individuals with ASD show reduced cognitive flexibility, which could reflect difficulty shifting from a previously learned response pattern or a failure to maintain a new response set. We examined different error types on a test of set-shifting completed by 60 individuals with ASD and 55 age- and nonverbal IQ-matched controls. Individuals with ASD were able to initially shift sets, but they exhibited difficulty maintaining new response sets. Difficulty with set maintenance was related to increased severity of RRBs. General difficulty maintaining new response sets and a heightened tendency to revert to old preferences may contribute to RRBs. | 25,234,483 | [
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Comparative analysis of histone H3 and H4 post-translational modifications of esophageal squamous cell carcinoma with different invasive capabilities. | Eukaryotic DNA is packaged into a chromatin with the help of four core histones (H2A, H2B, H3, and H4). Diverse histone post-translational modifications (PTMs) are hence involved in the regulation of gene transcription. However, how this regulation does work is still poorly understood and lacks details. Here we used the mass spectrometry-based proteomics approach to perform a comparative analysis of histone marks at a global level in two phenotypes of esophageal squamous cell carcinoma (ESCC) with different invasiveness. We obtained a comprehensive profiling of histone H3 and H4 PTMs including lysine methylation, acetylation and novel butyrylation. The correlation between histone marks and cancer invasive capabilities was further characterized and one distinguishable PTM, H4K79me2 was discovered and verified in this study. Immunohistochemistry analysis suggests that abnormal level of H4K79me2 may be related to poor survival of ESCC patients. Our results enrich the dataset of the feature pattern of global histone PTMs in ESCC cell lines. Core histone proteins, decorated by multiple biological significant protein post-translational modifications (PTMs) such as lysine acetylation and lysine methylation, are considered to regulate gene transcription and be associated with the development of cancer. Recent studies have further shown that global level of histone modifications is the potential hallmark of cancer to predict the clinical outcomes of human cancers. However, the regulation mechanism is largely unknown. Here we used the mass spectrometry based proteomics coupled with stable isotope labeling with amino acids in cell culture (SILAC) to characterize the global levels of histone marks in two phenotypes of esophageal squamous cell carcinoma (ESCC) cell lines with different invasive capabilities. To the best of our knowledge, it is the first report about the comparative analysis for histone marks of the different invasive ESCC cell lines. A significantly differential level of histone modification, H4K79me2, was determined and verified. Immunohistochemistry analysis further suggests that abnormal level of H4K79me2 may be related to poor survival of ESCC patients. Our results could contribute to understanding the different expressions of global histone PTMs in different invasive ESCC cell lines. | 25,234,497 | [
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Cervical conisation and the risk of preterm delivery: a retrospective matched pair analysis of a German cohort. | Since the routine screening program for cervical dysplasia by Pap smear was established in the early 1970s, the rate of cervical cancer has continually dropped. Even if a high percentage of cervical dysplasia shows spontaneous restitution, the only effective therapy for persisting cervical dysplasia is local ablation or excision which might be associated with an increased risk of preterm delivery in subsequent pregnancies. However, data from German patients are missing, so the aim of this study was to evaluate the risk of preterm delivery and associated risks in a cohort of patients who had undergone cervical conisation previous to their pregnancies. A total of 144 patients with conisation and subsequent pregnancy were identified. They were compared regarding week of delivery and preterm birth, fetal birth weight, fetal outcome and birth procedure (spontaneous delivery, vacuum extraction, primary and secondary cesarean section) with their matched partners. 135 patients with singleton pregnancies and their matched partners were evaluated in the final analysis. The mean age was 33.5 years. Comparing the case and control group we reached significant different results for week of delivery, but not preterm birth defined as birth prior to 37 weeks of gestation. Within this German cohort cervical conisation did not increase the risk for preterm birth, cesarean section or poor fetal outcome. We therefore conclude that cervical conisation is an appropriate method to treat women with cervical dysplasia also at childbearing age when prevention of cervical cancer is needed. | 25,234,516 | [
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Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America. | It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. | 25,234,519 | [
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Surgical management of the buccal bifurcation cyst: bone grafting as a treatment adjunct to enucleation and curettage. | The buccal bifurcation cyst (BBC) is a rare inflammatory odontogenic cyst of unknown etiology. It typically develops on the buccal aspect of the permanent mandibular first molar and occasionally on the permanent mandibular second molar in children 4 to 14 years old. Distinct clinical findings of the BBC include involvement of a vital partially or fully erupted mandibular first or second molar, swelling in the affected mandibular molar region, delayed or altered eruption pattern of the involved tooth, and an increase in periodontal pocket depth when the affected tooth is partially erupted. Specific radiographic features include a radiolucent lesion on the buccal aspect of the tooth involving the roots to a variable extent, tilting of the involved molar so that the root apices are toward the lingual cortical plate, an intact periodontal ligament space and lamina dura, a periosteal reaction on the buccal surface, and an intact inferior border of the mandible. The histopathology of the lesion has been described as similar to a radicular or inflammatory odontogenic cyst. Most of the current literature supports simple enucleation and curettage of the cyst without extraction of the involved tooth as the treatment of choice. This report presents 3 cases of BBCs that were treated with enucleation and curettage without extraction of the involved tooth, in addition to a bone graft placed primarily or secondarily as an adjunctive treatment approach to the current therapies. | 25,234,530 | [
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Computer-aided trauma simulation system with haptic feedback is easy and fast for oral-maxillofacial surgeons to learn and use. | Computer-assisted surgical (CAS) planning tools have become widely available in craniomaxillofacial surgery, but are time consuming and often require professional technical assistance to simulate a case. An initial oral and maxillofacial (OM) surgical user experience was evaluated with a newly developed CAS system featuring a bimanual sense of touch (haptic). Three volunteer OM surgeons received a 5-minute verbal introduction to the use of a newly developed haptic-enabled planning system. The surgeons were instructed to simulate mandibular fracture reductions of 3 clinical cases, within a 15-minute time limit and without a time limit, and complete a questionnaire to assess their subjective experience with the system. Standard landmarks and linear and angular measurements between the simulated results and the actual surgical outcome were compared. After the 5-minute instruction, all 3 surgeons were able to use the system independently. The analysis of standardized anatomic measurements showed that the simulation results within a 15-minute time limit were not significantly different from those without a time limit. Mean differences between measurements of surgical and simulated fracture reductions were within current resolution limitations in collision detection, segmentation of computed tomographic scans, and haptic devices. All 3 surgeons reported that the system was easy to learn and use and that they would be comfortable integrating it into their daily clinical practice for trauma cases. A CAS system with a haptic interface that capitalizes on touch and force feedback experience similar to operative procedures is fast and easy for OM surgeons to learn and use. | 25,234,531 | [
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RPTPs in axons, synapses and neurology. | Receptor-like protein tyrosine phosphatases represent a large protein family related to cell adhesion molecules, with diverse roles throughout neural development in vertebrates and invertebrates. This review focuses on their roles in axon growth, guidance and repair, as well as more recent findings demonstrating their key roles in pre-synaptic and post-synaptic maturation and function. These enzymes have been linked to memory and neuropsychiatric defects in loss-of-function rodent models, highlighting their potential as future drug targets. | 25,234,542 | [
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The length of the linker between the epidermal growth factor-like domains in factor VIIa is critical for a productive interaction with tissue factor. | Formation of the factor VIIa (FVIIa)-tissue factor (TF) complex triggers the blood coagulation cascade. Using a structure-based rationale, we investigated how the length of the linker region between the two epidermal growth factor (EGF)-like domains in FVIIa influences TF binding and the allosteric activity enhancement, as well as the interplay between the γ-carboxyglutamic acid (Gla)-containing and protease domains. Removal of two residues from the native linker was compatible with normal cofactor binding and accompanying stimulation of the enzymatic activity, as was extension by two (Gly-Ser) residues. In sharp contrast, truncation by three or four residues abolished the TF-mediated stabilization of the active conformation of FVIIa and abrogated TF-induced activity enhancement. In addition, FVIIa variants with short linkers associated 80-fold slower with soluble TF (sTF) as compared with wild-type FVIIa, resulting in a corresponding increase in the equilibrium dissociation constant. Molecular modeling suggested that the shortest FVIIa variants would have to be forced into a tense and energetically unfavorable conformation in order to be able to interact productively with TF, explaining our experimental observations. We also found a correlation between linker length and the residual intrinsic enzymatic activity of Ca(2+)-free FVIIa; stepwise truncation resulting in gradually higher activity with des(83-86)-FVIIa reaching the level of Gla-domainless FVIIa. The linker appears to determine the average distance between the negatively charged Gla domain and a structural element in the protease domain, presumably of opposite charge, and proximity has a negative impact on apo-FVIIa activity. | 25,234,571 | [
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Can biomarkers differentiate pain and no pain subgroups of nonverbal children with cerebral palsy? A preliminary investigation based on noninvasive saliva sampling. | Assessing and treating pain in nonverbal children with developmental disabilities are a clinical challenge. Current assessment approaches rely on clinical impression and behavioral rating scales completed by proxy report. Given the growing health relevance of the salivary metabolome, we undertook a translational-oriented feasibility study using proton nuclear magnetic resonance (NMR) spectroscopy and neuropeptide/cytokine/hormone detection to compare a set of salivary biomarkers relevant to nociception. Within-group observational design. Tertiary pediatric rehabilitation hospital. Ten nonverbal pediatric patients with cerebral palsy with and without pain. Unstimulated (passively collected) saliva was collected using oral swabs followed by perchloric acid extraction and analyzed on a Bruker Avance 700 MHz NMR spectrometer. We also measured salivary levels of several cytokines, chemokines, hormones, and neuropeptides. Partial least squares discriminant analysis showed separation of those children with/without pain for a number of different biomarkers. The majority of the salivary metabolite, neuropeptide, cytokine, and hormone levels were higher in children with pain vs no pain. The ease of collection and noninvasive manner in which the samples were collected and analyzed support the possibility of the regular predictive use of this novel biomarker-monitoring method in clinical practice. | 25,234,580 | [
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Efficacy of paced breathing for insomnia: enhances vagal activity and improves sleep quality. | Fourteen self-reported insomniacs (SRI) and 14 good sleepers (GS) had their cardiac neuronal activity assessed by heart rate variability (HRV) under controlled respiration at a slow frequency rate of 0.1 Hz, and a forced rate of 0.2 Hz during daytime rest. Nighttime sleep was measured by polysomnography. The SRI showed depressed high frequency power of HRV compared to the GS. An increased total power of HRV was observed among the SRI during slow, paced breathing compared with spontaneous breathing and 0.2 Hz. Sleep onset latency, number of awakenings, and awakening time during sleep were decreased and sleep efficiency was increased if SRI practiced slow, paced breathing exercises for 20 min before going to sleep. Our results indicate that there is autonomic dysfunction among insomniacs, especially in relation to vagal activity; however, this decreased vagal activity can be facilitated by practicing slow, paced breathing, thereby improving sleep quality. | 25,234,581 | [
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Photoionization mass spectrometric measurements of initial reaction pathways in low-temperature oxidation of 2,5-dimethylhexane. | Product formation from R + O2 reactions relevant to low-temperature autoignition chemistry was studied for 2,5-dimethylhexane, a symmetrically branched octane isomer, at 550 and 650 K using Cl-atom initiated oxidation and multiplexed photoionization mass spectrometry (MPIMS). Interpretation of time- and photon-energy-resolved mass spectra led to three specific results important to characterizing the initial oxidation steps: (1) quantified isomer-resolved branching ratios for HO2 + alkene channels; (2) 2,2,5,5-tetramethyltetrahydrofuran is formed in substantial yield from addition of O2 to tertiary 2,5-dimethylhex-2-yl followed by isomerization of the resulting ROO adduct to tertiary hydroperoxyalkyl (QOOH) and exhibits a positive dependence on temperature over the range covered leading to a higher flux relative to aggregate cyclic ether yield. The higher relative flux is explained by a 1,5-hydrogen atom shift reaction that converts the initial primary alkyl radical (2,5-dimethylhex-1-yl) to the tertiary alkyl radical 2,5-dimethylhex-2-yl, providing an additional source of tertiary alkyl radicals. Quantum-chemical and master-equation calculations of the unimolecular decomposition of the primary alkyl radical reveal that isomerization to the tertiary alkyl radical is the most favorable pathway, and is favored over O2-addition at 650 K under the conditions herein. The isomerization pathway to tertiary alkyl radicals therefore contributes an additional mechanism to 2,2,5,5-tetramethyltetrahydrofuran formation; (3) carbonyl species (acetone, propanal, and methylpropanal) consistent with β-scission of QOOH radicals were formed in significant yield, indicating unimolecular QOOH decomposition into carbonyl + alkene + OH. | 25,234,586 | [
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Towards an in vitro model mimicking the foreign body response: tailoring the surface properties of biomaterials to modulate extracellular matrix. | Despite various studies to minimize host reaction following a biomaterial implantation, an appealing strategy in regenerative medicine is to actively use such an immune response to trigger and control tissue regeneration. We have developed an in vitro model to modulate the host response by tuning biomaterials' surface properties through surface modifications techniques as a new strategy for tissue regeneration applications. Results showed tunable surface topography, roughness, wettability, and chemistry by varying treatment type and exposure, allowing for the first time to correlate the effect of these surface properties on cell attachment, morphology, strength and proliferation, as well as proinflammatory (IL-1β, IL-6) and antiinflammatory cytokines (TGF-β1, IL-10) secreted in medium, and protein expression of collagen and elastin. Surface microstructuring, derived from chloroform partial etching, increased surface roughness and oxygen content. This resulted in enhanced cell adhesion, strength and proliferation as well as a balance of soluble factors for optimum collagen and elastin synthesis for tissue regeneration. By linking surface parameters to cell activity, we could determine the fate of the regenerated tissue to create successful soft tissue-engineered replacement. | 25,234,587 | [
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Gamma-aminobutyric acid induces tumor cells apoptosis via GABABR1·β-arrestins·JNKs signaling module. | Gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in central nervous system, has yet been found to widely exist in tumor tissues to regulate tumor cells growth. However, the function of GABA on inducing tumor cells apoptosis and the potential mechanism are still unclear. In order to detect whether GABA via GABAB receptor GABABR1 would activate c-Jun N-terminal kinases (JNKs) to promote tumor cells apoptosis, co-immunoprecipitation assay was used to investigate the association of β-arrestins with GABABR1 and JNKs in the different four cancer cell lines. Our observation demonstrated that β-arrestins, in addition to their role in G protein-coupled receptors desensitization, had an additional function as adapter proteins to recruit JNKs to GABABR1, thereby conferring distinct enzymatic activities upon the receptor, which may trigger JNKs signal pathway involved in the regulation of cellular growth. Activated JNKs subsequently phosphorylated downstream c-Jun to transcribe a wide variety of pro-apoptotic genes. Additionally, GABA up-regulated the ratio of pro-apoptotic protein Bax to anti-apoptotic protein Bcl-2, and thus facilitated caspase-3 cleavage, leading to tumor cells apoptosis in a mitochondrial-dependent pathway. In contrast, GABABR antagonist CGP35348 reversed GABA-induced JNKs phosphorylation and its downstream proteins activation, which consequently restrained tumor cells apoptosis. Taken together, our study suggested that GABA via its receptor GABABR1 recruited β-arrestins to facilitate the activation of JNKs cascade, resulting in tumor cells growth inhibition. | 25,234,615 | [
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Evaluating cost when selecting performance reference compounds for the environmental deployment of polyethylene passive samplers. | A challenge in environmental passive sampling is determining when equilibrium is achieved between the sampler, target contaminants, and environmental phases. A common approach is the use of performance reference compounds (PRCs) to estimate target contaminant sampling rates and indicate degree of sampler equilibrium. One logistical issue associated with using PRCs is their sometimes exorbitant cost. To address PRC expense, this investigation 1) compared the performance of inexpensive PRCs (deuterated PAHs) and expensive PRCs ((13) C-labeled PCBs) to estimate dissolved PCB concentrations in freshwater and marine deployments, and 2) evaluated the use of smaller quantities of PRC relative to regular amounts used for estimating dissolved PAH and PCB concentrations. Saltwater and freshwater site average differences between total dissolved PCB concentrations calculated using the 2 classes of PRCs was 34 pg/L (20%) and 340 pg/L (51%), respectively, and in some deployments, statistical differences in PCB concentrations generated by the 2 types of PRCs were detected. However, no statistical differences were detected between total dissolved PAH and PCB for the 3 quantities of PRCs. In both investigations, individual dissolved PCB congeners and PAH compounds demonstrated comparable behavior as those expressed as total PCB or PAH dissolved concentrations. This research provides evidence that in some applications passive sampling using inexpensive and smaller quantities of PRCs can yield cost savings of approximately 75%. This approach appears most promising in the marine water column and when focusing on dissolved concentrations of low and medium molecular weight congeners or total PCBs. | 25,234,621 | [
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Human microRNA-24 modulates highly pathogenic avian-origin H5N1 influenza A virus infection in A549 cells by targeting secretory pathway furin. | A common critical cellular event that many human enveloped viruses share is the requirement for proteolytic cleavage of the viral glycoprotein by furin in the host secretory pathway. For example, the furin-dependent proteolytic activation of highly pathogenic (HP) influenza A (infA) H5 and H7 haemagglutinin precursor (HA0) subtypes is critical for yielding fusion-competent infectious virions. In this study, we hypothesized that viral hijacking of the furin pathway by HP infA viruses to permit cleavage of HA0 could represent a novel molecular mechanism controlling the dynamic production of fusion-competent infectious virus particles during the viral life cycle. We explored the biological role of a newly identified furin-directed human microRNA, miR-24, in this process as a potential post-transcriptional regulator of the furin-mediated activation of HA0 and production of fusion-competent virions in the host secretory pathway. We report that miR-24 and furin are differentially expressed in human A549 cells infected with HP avian-origin infA H5N1. Using miR-24 mimics, we demonstrated a robust decrease in both furin mRNA levels and intracellular furin activity in A549 cells. Importantly, pretreatment of A549 cells with miR-24 mimicked these results: a robust decrease of H5N1 infectious virions and a complete block of H5N1 virus spread that was not observed in A549 cells infected with low-pathogenicity swine-origin infA H1N1 virus. Our results suggest that viral-specific downregulation of furin-directed microRNAs such as miR-24 during the life cycle of HP infA viruses may represent a novel regulatory mechanism that governs furin-mediated proteolytic activation of HA0 glycoproteins and production of infectious virions. | 25,234,642 | [
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Differential shift in spatial bias over time depends on observers׳ initial bias: Observer subtypes, or regression to the mean? | Healthy subjects typically exhibit a subtle bias of visuospatial attention favouring left space that is commonly termed 'pseudoneglect'. This bias is attenuated, or shifted rightwards, with decreasing alertness over time, consistent with theoretical models proposing that pseudoneglect is a result of the right hemisphere׳s dominance in regulating attention. Although this 'time-on-task effect' for spatial bias is observed when averaging across whole samples of healthy participants, Benwell, C. S. Y., Thut, G., Learmonth, G., & Harvey, M. (2013b). Spatial attention: differential shifts in pseudoneglect direction with time-on-task and initial bias support the idea of observer subtypes. Neuropsychologia, 51(13), 2747-2756 recently presented evidence that the direction and magnitude of bias exhibited by the participant early in the task (left biased, no bias, or right biased) were stable traits that predicted the direction of the subsequent time-on-task shift in spatial bias. That is, the spatial bias of participants who were initially left biased shifted in a rightward direction with time, whereas that of participants who were initially right biased shifted in a leftward direction. If valid, the data of Benwell et al. are potentially important and may demand a re-evaluation of current models of the neural networks governing spatial attention. Here we use two novel spatial attention tasks in an attempt to confirm the results of Benwell et al. We show that rather than being indicative of true participant subtypes, these data patterns are likely driven, at least in part, by 'regression towards the mean' arising from the analysis method employed. Although evidence supports the contention that trait-like individual differences in spatial bias exist within the healthy population, no clear evidence is yet available for participant/observer subtypes in the direction of time-on-task shift in spatial biases. | 25,234,646 | [
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Pharmacokinetic and pharmacodynamic evaluation of elosulfase alfa, an enzyme replacement therapy in patients with Morquio A syndrome. | Morquio A syndrome (mucopolysaccharidosis IVA; MPS IVA) is a lysosomal storage disorder caused by deficiency of N-acetylgalactosamine-6-sulfatase, an enzyme required for degradation of the glycosaminoglycan keratan sulfate. Enzyme replacement therapy with elosulfase alfa provides a potential therapy for Morquio A syndrome. We analyzed the pharmacokinetics and pharmacodynamics of elosulfase alfa in Morquio A patients from a phase III clinical trial. In a randomized double-blind study, elosulfase alfa at 2.0 mg/kg was administrated weekly or every other week for 24 weeks. Pharmacokinetic parameters of elosulfase alfa were determined at weeks 0 and 22 by non-compartmental analysis. Safety was assessed throughout the study. The relationship of pharmacokinetic parameters to patient demographics, pharmacodynamic assessments, immunogenicity, and efficacy and safety outcomes were assessed graphically by treatment group. Elosulfase alfa exposure and half-life (t(½)) increased for both dose regimens during the study. There appeared to be no consistent trend between drug clearance (CL) and patient's sex, race, body weight, or age. All patients developed anti-drug antibodies, but no association was noted between total antibody titer and CL. In contrast, positive neutralizing antibody (NAb) status appeared to associate with decreased CL and prolonged t(½) for patients in the cohort dosed weekly. NAb may interfere with receptor-mediated cellular uptake and lead to increased circulation time of elosulfase alfa. Despite the association between NAb and decreased drug clearance, neither dosing cohort showed associations between drug exposure and change in urinary keratan sulfate, 6-min walk test distances, or the occurrence of adverse events. | 25,234,648 | [
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Tongue carcinoma infrequently harbor common actionable genetic alterations. | Oral tongue squamous cell carcinomas (TSCC) are a unique subset of head and neck cancers with a distinct demographic profile, where up to half of the cases are never smokers. A small proportion of patients with OSCC are known to respond to EGFR TKI. We used a high-sensitivity mass spectrometry-based mutation profiling platform to determine the EGFR mutation status, as well as other actionable alterations in a series of Asian TSCC. 66 TSCC patients treated between 1998-2009 with complete clinico-pathologic data were included in this study. Somatic mutation profiling was performed using Sequenom LungCarta v1.0, and correlated with clinical parameters. Mutations were identified in 20/66(30.3%) of samples and involved TP53, STK11, MET, PIK3CA, BRAF and NRF2. No activating EGFR mutations or KRAS mutations were discovered in our series, where just over a third were never smokers. The most common mutations were in p53 (10.6%; n = 7) and MET (10.6%, n = 11) followed by STK11 (9.1%, n = 6) and PIK3CA (4.5%, n = 3). BRAF and NRF2 mutations, which are novel in TSCC, were demonstrated in one sample each. There was no significant correlation between overall mutation status and smoking history (p = 0.967) or age (p = 0.360). Positive MET alteration was associated with poorer loco-regional recurrence free survival (LRFS) of 11 months [vs 90 months in MET-negative group (p = 0.008)]. None of the other mutations were significantly correlated with LRFS or overall survival. Four of these tumors were propagated as immortalized cell lines and demonstrated the same mutations as the original tumor. Using the Sequenom multiplexed LungCarta panel, we identified mutations in 6 genes, TP53, STK11, MET, PIK3CA, BRAF and NRF2, with the notable absence of EGFR and HER2 mutations in our series of Asian OSCC. Primary cell line models recapitulated the mutation profiles of the original primary tumours and provide an invaluable resource for experimental cancer therapeutics. | 25,234,657 | [
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Characteristics associated with the presence and development of extra-articular manifestations in ankylosing spondylitis: 12-year results from OASIS. | The aim of this study was to identify characteristics associated with the presence and development of extra-articular manifestations (EAMs) in a prevalence cohort of patients with AS. Twelve-year follow-up data from the Outcome in Ankylosing Spondylitis International Study (OASIS) were used. In addition, medical charts were checked for the presence of acute anterior uveitis (AAU), IBD and psoriasis. Demographic, clinical and radiographic characteristics associated with the presence of (any) EAM at baseline or new development during follow-up were identified. Two hundred and sixteen patients were included [mean age 43.6 years (s.d. 12.7), 154 (71%) men, mean symptom duration 20.5 years (s.d. 11.7), mean follow-up 8.3 years (s.d. 4.3)]. At baseline, 39 (18%) patients had AAU, 15 (7%) had IBD and 9 (4%) had psoriasis. The history of AAU was univariably associated with increased age [odds ratio (OR) 1.04 (95% CI 1.01, 1.07)], longer symptom duration [OR 1.05 (95% CI 1.02, 1.08)] and more radiographic damage [OR 1.02 (95% CI 1.00, 1.04)]. The history of psoriasis was associated with greater age [OR 1.05 (95% CI 1.00, 1.11)] and lower CRP [OR 0.77 (95% CI 0.59, 1.00)]. At follow-up, 27 patients developed a new EAM. Newly developed IBD was associated with a higher time-varying AS Disease Activity Score [hazard ratio (HR) 2.80 (95% CI 1.43, 5.52)], worse physical function [HR 1.40 (95% CI 1.09, 1.80)] and worse patient global well-being [HR 1.46 (95% CI 1.10, 1.93)]. Newly developed AAU was associated with an elevated time-varying CRP [HR 1.02 (95% CI 1.01, 1.04)]. Development of EAMs was infrequent in this cohort, despite relatively long follow-up. In particular, markers of disease activity were associated with the development of IBD. | 25,234,663 | [
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Outcomes of primary percutaneous coronary intervention in ST-segment elevation myocardial infarction patients with previous coronary bypass surgery. | This study sought to determine the contemporary clinical characteristics and outcomes of patients with ST-segment elevation myocardial infarction (STEMI) and previous coronary artery bypass graft (CABG), including those with a saphenous vein graft culprit lesion. The outcome of STEMI patients with previous CABG is reported to be inferior to those without previous CABG, but limited data is available from the primary percutaneous coronary intervention era. Data was extracted from a large, regional STEMI system's prospective database, which contained 3,542 unique STEMI episodes from March 4, 2003 through April 22, 2012. Previous CABG was present in 249 patients (7%). Despite higher comorbidity, patients with versus those without previous CABG had similar in-hospital (4.8% vs. 5.2%; p = 0.82) and 1-year (10.8% vs. 9.1%; p = 0.36) mortality, but 5-year (24.9% vs. 14.2%; p < 0.001) mortality was higher. Patients with previous CABG have similar door-to-balloon times. The culprit vessel was the saphenous vein graft in 84 patients (34%), a native vessel in 104 (42%), with no clear culprit in 59 (24%). The left internal mammary artery graft was not a culprit in any patient. Mortality at 30 days (8.3% vs. 3.9% vs. 1.7%, p = 0.19) and 1 year (14.3% vs. 9.0% vs. 6.8%; p = 0.35) was higher (but not statistically) with a saphenous vein graft culprit and was equivalent at 5 years (25.0% vs. 26.0% vs. 20.3%; p = 0.71). Patients with previous CABG treated in a regional STEMI system have similar outcomes as patients without previous CABG, although 5-year mortality is higher. The most common culprit location was a native vessel (42%). Outcomes have improved significantly compared with historical reports. | 25,234,670 | [
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Sustained heterozygosity across a self-incompatibility locus in an inbred ascidian. | Because self-incompatibility loci are maintained heterozygous and recombination within self-incompatibility loci would be disadvantageous, self-incompatibility loci are thought to contribute to structural and functional differentiation of chromosomes. Although the hermaphrodite chordate, Ciona intestinalis, has two self-incompatibility genes, this incompatibility system is incomplete and self-fertilization occurs under laboratory conditions. Here, we established an inbred strain of C. intestinalis by repeated self-fertilization. Decoding genome sequences of sibling animals of this strain identified a 2.4-Mbheterozygous region on chromosome 7. A self-incompatibility gene, Themis-B, was encoded within this region. This observation implied that this self-incompatibility locus and the linkage disequilibrium of its flanking region contribute to the formation of the 2.4-Mb heterozygous region, probably through recombination suppression. We showed that different individuals in natural populations had different numbers and different combinations of Themis-B variants, and that the rate of self-fertilization varied among these animals. Our result explains why self-fertilization occurs under laboratory conditions. It also supports the concept that the Themis-B locus is preferentially retained heterozygous in the inbred line and contributes to the formation of the 2.4-Mb heterozygous region. High structural variations might suppress recombination, and this long heterozygous region might represent a preliminary stage of structural differentiation of chromosomes. | 25,234,703 | [
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Characterization of natural organic colorants in historical and art objects by high-performance liquid chromatography. | High-performance liquid chromatography plays an important role in analysis of historical organic colorants. A number of papers have been published in this field over the last 30 years. Classification of the most commonly used natural dyes and an overview of high-performance liquid chromatography methods with main focus on recent works (2008 to the beginning of 2014) are provided. The review deals with an entire analytical protocol covering sample preparation, chromatographic separation, and suitable detection (UV/visible and fluorescent spectroscopy and mass spectrometric techniques). High-performance liquid chromatography has been successfully used in the complete characterization of some organic dyestuffs present in historical and art objects. The possibilities and difficulties for identification of natural sources of historical colorants are also discussed. | 25,234,708 | [
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MiR99a modulates MMP7 and MMP13 to regulate invasiveness of Kaposi's sarcoma. | Matrix metalloproteinases (MMPs) and microRNAs (miRNAs) are associated with Kaposi's sarcoma (KS) tumorigenesis. To date, the molecular basis underlying crosstalk of MMPs and miRNAs in KS remains unexplored. From the resected KS samples, we detected significant correlation of miRNA99a (miR99a), with MMP7 and MMP13, but not with MMP9. To define whether a causal link exists, we used a human KS line, SLK, to study the molecular basis of miR99a and activation of MMP7, MMP9, and MMP13. We found that overexpression of miR99a in SLK cells decreased MMP7 and MMP13, but not MMP9. Similarly, MiR99a inhibition in SLK cells activated MMP7 and MMP13, but did not affect expression of MMP9. These data suggest that MMP7 and MMP13 seem to be regulated by miR99a, while MMP9 seems to be regulated in a miR99a-independent manner. Inhibition of PI3k/Akt signaling pathway significantly abolished the effect of miR99a-knockdown on MMP7, but not MMP13 activation, while inhibition of ERK/MAPK signaling pathway significantly abolished the effect of miR99a-knockdown on MMP13, but not MMP7 activation. Taken together, our data suggest that miR99a inhibits MMP7 and MMP13 through PI3k/Akt and ERK/MAPK signaling pathway, respectively, in KS. Thus, miR99a, MMP7, and MMP13 appear to be promising therapeutic targets for preventing the metastasis of KS. | 25,234,715 | [
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New insights in cellular and molecular aspects of BM niche in chronic myelogenous leukemia. | Hematoproliferative neoplasias like chronic myelogenous leukemia (CML) progressively affect bone marrow niche; however, there are only few specific clinical markers for prediction of disease progression. Here, we review the myeloproliferative niche and molecular changes including signaling pathways as well as microRNA (miRNA) in CML in order to better understand the therapeutic approaches. CML is a three-stage myeloproliferative disorder caused by reciprocal translocation between chromosome 9 and 22. There has been a new interest on treatment of this disorder. Therefore, in order to develop the appropriate therapy, an analysis of the molecular changes involved in malignant cells can be effective. A review of the signaling pathways, miRNA, and related targets can be helpful for better understanding of molecular pathogenesis of CML. Characterizing malignant cells and molecular changes with a focus on their targets may help researchers use molecular targets as effective therapeutic means for CML. On the other hand, interactions between leukemic stem cells and CML niche will help researchers investigate the causes of drug resistance in this disease. | 25,234,716 | [
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Overexpression of CaDSR6 increases tolerance to drought and salt stresses in transgenic Arabidopsis plants. | The partial CaDSR6 (Capsicum annuum Drought Stress Responsive 6) cDNA was previously identified as a drought-induced gene in hot pepper root tissues. However, the cellular role of CaDSR6 with regard to drought stress tolerance was unknown. In this report, full-length CaDSR6 cDNA was isolated. The deduced CaDSR6 protein was composed of 234 amino acids and contained an approximately 30 amino acid-long Asp-rich domain in its central region. This Asp-rich domain was highly conserved in all plant DSR6 homologs identified and shared a sequence identity with the N-terminal regions of yeast p23(fyp) and human hTCTP, which contain Rab protein binding sites. Transgenic Arabidopsis plants overexpressing CaDSR6 (35S:CaDSR6-sGFP) were tolerant to high salinity, as identified by more vigorous root growth and higher levels of total chlorophyll than wild type plants. CaDSR6-overexpressors were also more tolerant to drought stress compared to wild type plants. The 35S:CaDSR6-sGFP leaves retained their water content and chlorophyll more efficiently than wild type leaves in response to dehydration stress. The expression of drought-induced marker genes, such as RD20, RD22, RD26, RD29A, RD29B, RAB18, KIN2, ABF3, and ABI5, was markedly increased in CaDSR6-overexpressing plants relative to wild type plants under both normal and drought conditions. These results suggest that overexpression of CaDSR6 is associated with increased levels of stress-induced genes, which, in turn, conferred a drought tolerant phenotype in transgenic Arabidopsis plants. Overall, our data suggest that CaDSR6 plays a positive role in the response to drought and salt stresses. | 25,234,727 | [
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Comparative safety profiles of intravitreal bevacizumab, ranibizumab and pegaptanib: the analysis of the WHO database of adverse drug reactions. | The purpose of this study is to conduct a comparative analysis of the suspected adverse drug reactions (ADRs) associated with intravitreal bevacizumab, ranibizumab and pegaptanib in the WHO database in order to have a real-life information on these drugs, which now is only based on data coming from clinical trials. ADR reports for intravitreal use of bevacizumab, ranibizumab and pegaptanib from January 2002 to December 2012 were selected from the WHO-VigiBase. Reporting odds ratio (ROR) with confidence interval of 95 % and p value was calculated. The analysis was performed for drug-reaction pairs. The Medical Dictionary for Regulatory Activities (MedDRA) terminology for ADRs was used. The analysis was performed on 3180 reports corresponding to 7753 drug-reaction pairs. Significant RORs for endophthalmitis and uveitis (1.90, 95 % confidence interval (CI) 1.48-2.43, and 10.62, 6.62-17.05, respectively) were retrieved for bevacizumab, and cerebrovascular accident and myocardial infarction produced significant ROR (1.54, 1.14-2.10 and 1.73, 1.18-2.53, respectively) for ranibizumab. Pegaptanib was significantly associated with visual impairment (1.98, 1.12-3.5, p = 0.02), nausea (3.29, 1.57-6.86, p < 0.001), vomiting (2.91, 1.2-7.07, p = 0.01) and drug hypersensitivity (8.75, 3.1-24.66, p < 0.001). Our data showed an elevated disproportionality for cardiovascular ADRs in patients treated with ranibizumab and for infective ocular reactions in those treated with bevacizumab. No relevant safety issues were identified for pegaptanib. These findings suggest bevacizumab as a suitable choice for AMD therapy due to its effectiveness similar to that of ranibizumab, its favourable safety profile and for its lower cost. | 25,234,795 | [
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Characterisation and impact of reported and unreported exacerbations: results from ATTAIN. | The frequency and impact of exacerbations identified using healthcare resource utilisation (HCRU) or the EXAcerbations of Chronic pulmonary disease Tool (EXACT) were compared prospectively in a 24-week, phase III trial (ATTAIN). Patients with moderate-to-severe chronic obstructive pulmonary disease received twice-daily aclidinium 200 μg, aclidinium 400 μg or placebo. All HCRU events were reported to physicians. "EXACT-identified" events were categorised as "EXACT-reported" (detected by EXACT and reported to the physician) and "EXACT-unreported" (detected but not reported). Health status was measured using the St George's Respiratory Questionnaire (SGRQ). Annualised EXACT-identified event rates were higher in all study arms (placebo 1.39, aclidinium 200 μg 1.00 and aclidinium 400 μg 0.98 per patient per year) versus HCRU (placebo 0.60, aclidinium 200 μg 0.43 and aclidinium 400 μg 0.40 per patient per year). Concordance between methods was low (kappa 0.16). Aclidinium reduced EXACT-identified events (rate ratio versus placebo: aclidinium 200 μg 0.72 and aclidinium 400 μg 0.71; both p<0.05); HCRU events were similarly reduced. At week 24, SGRQ scores improved (-6.6 versus baseline) in patients with no event during weeks 1-12; improvements were significantly smaller in patients with HCRU events (-3.4; p=0.036) or EXACT-unreported events (-3.0; p=0.002). Unreported events were more frequent than reported events. Both had similar negative impact on health status. Aclidinium reduced the frequency of both types of event. | 25,234,803 | [
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Mexican immigrant women reaching out: the role of informal networks in the process of seeking help for intimate partner violence. | More inquiry is needed into how Mexican immigrant survivors of intimate partner violence (IPV) are seeking help, to improve interventions designed to reach this isolated and vulnerable population. This grounded theory study, using a sample of 29 Mexican immigrant survivors of IPV and 15 key informants, examines the help-seeking process. Findings indicate that informal networks, particularly family and female friends, play a critical role in providing assistance and linking women to formal services. These findings have implications for the delivery of formal domestic violence services to this community as well as the response of police and other formal service systems. | 25,234,812 | [
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Brown skin disease: A syndrome of dysecdysis in Puerto Rican crested toads (Peltophryne lemur). | The endangered Puerto Rican crested toad (Peltophryne [Bufo] lemur) has been held and bred in zoos for release into protected areas in Puerto Rico since 1982. In 2004, several cases of a novel syndrome of skin changes in toads were noticed at the Toronto Zoo. A total of 21 toads were found to have similar lesions and the condition has been seen in several other groups of toads in subsequent years. Affected toads show an uncharacteristic sheen of dark-brown leathery skin, followed by recurring dysecdysis, reduced appetite, weight loss, and death from secondary causes. Histologically the condition is characterized by epithelial hyperplasia and hyperkeratosis, ulceration, and the presence of superficial mats of bacterial and fungal agents. No etiology has been identified and to date toads have not permanently responded to treatment with various pharmaceutical and nutritional therapies. | 25,234,808 | [
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Coronary endothelial dysfunction is associated with inflammation and vasa vasorum proliferation in patients with early atherosclerosis. | Endothelial dysfunction is an early manifestation of atherosclerosis. Inflammation and vasa vasorum play a pivotal role in the pathophysiology of plaque initiation, development, and complications. Optical coherence tomography allows high-resolution imaging of tissue microstructure. Therefore, the aim of this study was to test the hypothesis that segments with endothelial dysfunction show macrophages and vasa vasorum in patients with early coronary artery disease. Optical coherence tomography images were obtained from 40 patients with mild coronary atherosclerosis who underwent coronary endothelial function assessment. Optical coherence tomography findings, including macrophages and microchannels, were evaluated in 76 coronary segments corresponding to those in endothelial response to acetylcholine. Coronary artery diameter change in response to acetylcholine was more severe in segments showing macrophages (-17.7±14.7% versus -6.3±13.9%; P<0.01) and microchannels (-15.9±15.9% versus -6.4±13.5%; P<0.01) than those without. There were increasing trends of the prevalence of macrophages and microchannels with endothelial dysfunction as stratified by quartiles of coronary artery diameter change (P<0.01 and P=0.02 for trend, respectively). In particular, segments with both macrophages and microchannels (n=12) tended to have worse endothelial function than those with macrophages alone (n=15) and microchannels alone (n=15; -22.1±14.6% versus -10.9±15.6% and -10.9±15.6%; P=0.07 and P=0.06, respectively). Epicardial endothelial dysfunction was associated with optical coherence tomography -identified macrophages and microchannels in mild coronary atherosclerosis. The current study further supports the role of inflammation and vasa vasorum proliferation in the early stage of coronary atherosclerosis. | 25,234,815 | [
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Self-assembling lipid modified glycol-split heparin nanoparticles suppress lipopolysaccharide-induced inflammation through TLR4-NF-κB signaling. | Self-assembling heparin nanoparticles have attracted much attention as promising drug carriers for various drugs, genes and imaging agents. In the present investigation, we found that heparin nanoparticles are selective Toll-like receptor 4 (TLR-4) antagonists and have a much greater anti-inflammatory effect than native heparin. More specifically, we developed self-assembling nanoparticles composed of glycol-split heparin/D-erythro-sphingosine conjugates (NAHNP), characterized their physicochemical properties and anti-inflammatory effect in vitro. Unlike native heparin, NAHNP significantly inhibited lipopolysaccharide-induced activation of MyD88-dependent NF-κB signaling pathway and production of pro-inflammatory cytokines such as TNF-alpha from mouse macrophages with IC50 = 0.019 mg/mL. Furthermore, we investigated the structure-activity relationship of the conjugates and identified the length of attached alkyl chains of d-erythro-sphingosine to be critical for anti-inflammatory effect. Decrease in alkyl chain length of NAHNP resulted in loss of inhibitory activity. In line with these findings, 6-O-sulfate groups of D-glucosamine residue were essential for effective inhibition, while removal of 2-O-sulfo and 3-O-sulfo groups as well as replacement of N-sulfo groups with N-acetyl did not alter anti-inflammatory activity. Therefore, NAHNP would be a promising candidate in acute and chronic inflammatory disorders, in addition to the nature of a drug carrier. | 25,234,820 | [
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Assessment of myocardial infarct size with body surface potential mapping: validation against contrast-enhanced cardiac magnetic resonance imaging. | Assessment of myocardial infarct (MI) size is important for therapeutic and prognostic reasons. We used body surface potential mapping (BSPM) to evaluate whether single-lead electrocardiographic variables can assess MI size. We performed BSPM with 120 leads covering the front and back chest (plus limb leads) on 57 patients at different phases of MI: acutely, during healing, and in the chronic phase. Final MI size was determined by contrast-enhanced cardiac magnetic resonance imaging (DE-CMR) and correlated with various computed depolarization- and repolarization-phase BSPM variables. We also calculated correlations between BSPM variables and enzymatic MI size (peak CK-MBm). BSPM variables reflecting the Q- and R wave showed strong correlations with MI size at all stages of MI. R width performed the best, showing its strongest correlation with MI size on the upper right back, there representing the width of the "reciprocal Q wave" (r = 0.64-0.71 for DE-CMR, r = 0.57-0.64 for CK-MBm, P < 0.0001). Repolarization-phase variables showed only weak correlations with MI size in the acute phase, but these correlations improved during MI healing. T-wave variables and the QRSSTT integral showed their best correlations with DE-CMR defined MI size on the precordial area, at best r = -0.57, P < 0.0001 in the chronic phase. The best performing BSPM variables could differentiate between large and small infarcts at all stages of MI. Computed, single-lead electrocardiographic variables can estimate the final infarct size at all stages of MI, and differentiate large infarcts from small. | 25,234,825 | [
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Outcomes of HER2-positive early breast cancer patients in the pre-trastuzumab and trastuzumab eras: a real-world multicenter observational analysis. The RETROHER study. | Addition of trastuzumab to adjuvant chemotherapy has dramatically reduced the risk of recurrence and has become the standard of care for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer patients. Since most data on trastuzumab benefits come from clinical trials, conducted in selected patient populations, we performed a retrospective analysis of HER2-positive early breast cancer patients treated in the "pre-trastuzumab" and "trastuzumab" eras, with the aim to determine patients' outcomes in real-world practice. 925 consecutive HER2-positive breast cancer patients treated with adjuvant chemotherapy in ten Italian oncologic centers were identified. Patients who had received adjuvant chemotherapy alone (cohort A, 352 patients), and patients who had received adjuvant chemotherapy followed or combined with trastuzumab (cohort B, 573 patients) were analyzed. Relapse rate at 3 years, relapse-free survival, and overall survival were significantly more unfavorable in the cohort A than in the cohort B (p < 0.0001). In multivariate analysis, factors related to relapse were younger age, advanced stage at diagnosis, absence of hormonal and of trastuzumab therapy. The benefit derived from the addition of trastuzumab was independent of nodal status and hormonal receptors expression. A subgroup analysis including 163 "triple positive" tumors with high levels of estrogen and progesterone receptor (TP50) suggested that addition of trastuzumab to adjuvant chemotherapy and hormonal therapy did not translate into better outcomes. In our analysis, trastuzumab benefit was confirmed in all but a small subset of TP50 tumors subgroups. In this subset further investigations are needed. | 25,234,842 | [
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Photoelectrochemical reduction of aqueous protons with a CuO|CuBi2O4 heterojunction under visible light irradiation. | A p-type heterojunction photoelectrode consisting of platinized CuBi2O4 layered on a CuO film was prepared. The CuO|CuBi2O4|Pt electrode photo-generates H2 in pH neutral aqueous solution during visible light irradiation and exhibits a substantially enhanced photocurrent compared to CuO|Pt and CuBi2O4|Pt electrodes. Reduced electron-hole recombination by the band offsets in the heterostructure is responsible for the improved photoelectrochemical performance of CuO|CuBi2O4 with a small band-gap of approximately 1.5 eV. | 25,234,857 | [
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Pleuroparenchymal fibroelastosis and non-specific interstitial pneumonia: frequent pulmonary sequelae of haematopoietic stem cell transplantation. | Pulmonary sequelae, reported as chronic graft-versus-host disease (cGVHD), of haematopoietic stem cell transplantation (HSCT) include constrictive bronchiolitis obliterans (CBO), lymphocytic bronchiolitis (LB), and veno-occlusive disease (VOD); recently, pleuroparenchymal fibroelastosis (PPFE) has also been described in bone marrow transplant recipients. The histological features of pulmonary HSCT sequelae have not been described systematically. The aim of the study was to review and identify the histological features of PPFE after bone marrow transplant. A retrospective review of 20 patients who underwent lung transplantation for pulmonary disease following HSCT between 2004 and 2013 was conducted. The patient age at transplantation ranged from 8 years to 57 years (median, 27.5 years). Fifteen patients had cGVHD in other organs (skin, nine; liver, six; salivary gland, six). Lung transplantation was performed at a median of 4.6 years (range, 1.2-14.8 years) post-HSCT. Histologically, all cases had CBO, with concurrent LB in 10, and VOD in three. PPFE was identified in 15 cases (75%), with subpleural (15), paraseptal (11) and centrilobular (13) distributions; and non-specific interstitial pneumonia (NSIP) was identified in 15 cases (75%), with fibrotic (nine) and cellular (six) patterns. PPFE was distributed in all lobes, with a predominance in the upper lobe. NSIP was mostly focal, with two cases having diffuse involvement. PPFE and NSIP were frequently seen in HSCT patients. Possible causes may include reactions to drugs or radiation, or cGVHD. | 25,234,860 | [
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Acoustic mode coupling induced by nonlinear internal waves: evaluation of the mode coupling matrices and applications. | This paper applies the mode coupling equation to calculate the mode-coupling matrix for nonlinear internal waves appearing as a train of solitons. The calculation is applied to an individual soliton up to second order expansion in sound speed perturbation in the Dyson series. The expansion is valid so long as the fractional sound speed change due to a single soliton, integrated over range and depth, times the wavenumber is smaller than unity. Scattering between the solitons are included by coupling the mode coupling matrices between the solitons. Acoustic fields calculated using this mode-coupling matrix formulation are compared with that obtained using a parabolic equation (PE) code. The results agree very well in terms of the depth integrated acoustic energy at the receivers for moving solitary internal waves. The advantages of using the proposed approach are: (1) The effects of mode coupling can be studied as a function of range and time as the solitons travel along the propagation path, and (2) it allows speedy calculations of sound propagation through a packet or packets of solitons saving orders of magnitude computations compared with the PE code. The mode coupling theory is applied to at-sea data to illustrate the underlying physics. | 25,234,871 | [
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Examining the robustness of automated aural classification of active sonar echoes. | Active sonar systems are used to detect underwater man-made objects of interest (targets) that are too quiet to be reliably detected with passive sonar. Performance of active sonar can be degraded by false alarms caused by echoes returned from geological seabed structures (clutter) in shallow regions. To reduce false alarms, a method of distinguishing target echoes from clutter echoes is required. Research has demonstrated that perceptual-based signal features similar to those employed in the human auditory system can be used to automatically discriminate between target and clutter echoes, thereby reducing the number of false alarms and improving sonar performance. An active sonar experiment on the Malta Plateau in the Mediterranean Sea was conducted during the Clutter07 sea trial and repeated during the Clutter09 sea trial. The dataset consists of more than 95,000 pulse-compressed echoes returned from two targets and many geological clutter objects. These echoes were processed using an automatic classifier that quantifies the timbre of each echo using a number of perceptual signal features. Using echoes from 2007, the aural classifier was trained to establish a boundary between targets and clutter in the feature space. Temporal robustness was then investigated by testing the classifier on echoes from the 2009 experiment. | 25,234,872 | [
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The role of syntax in maintaining the integrity of streams of speech. | This study examined the ability of listeners to utilize syntactic structure to extract a target stream of speech from among competing sounds. Target talkers were identified by voice or location, which was held constant throughout a test utterance, and paired with correct or incorrect (random word order) target sentence syntax. Both voice and location provided reliable cues for identifying target speech even when other features varied unpredictably. The target sentences were masked either by predominantly energetic maskers (noise bursts) or by predominantly informational maskers (similar speech in random word order). When the maskers were noise bursts, target sentence syntax had relatively minor effects on identification performance. However, when the maskers were other talkers, correct target sentence syntax resulted in significantly better speech identification performance than incorrect syntax. Furthermore, conformance to correct syntax alone was sufficient to accurately identify the target speech. The results were interpreted as supporting the idea that the predictability of the elements comprising streams of speech, as manifested by syntactic structure, is an important factor in binding words together into coherent streams. Furthermore, these findings suggest that predictability is particularly important for maintaining the coherence of an auditory stream over time under conditions high in informational masking. | 25,234,885 | [
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Dynamic adjustment of echolocation pulse structure of big-footed myotis (Myotis macrodactylus) in response to different habitats. | Studying relationships between characteristics of sonar pulses and habitat clutter level is important for the understanding of signal design in bat echolocation. However, most studies have focused on overall spectral and temporal parameters of such vocalizations, with focus less on potential variation in frequency modulation rates (MRs) occurring within each pulse. In the current study, frequency modulation (FM) characteristics were examined in echolocation pulses recorded from big-footed myotis (Myotis macrodactylus) bats as these animals searched for prey in five habitats differing in relative clutter level. Pulses were analyzed using ten parameters, including four structure-related characters which were derived by dividing each pulse into three elements based on two knees in the FM sweep. Results showed that overall frequency, pulse duration, and MR all varied across habitat. The strongest effects were found for MR in the body of the pulse, implying that this particular component plays a major role as M. macrodactylus, and potentially other bat species, adjust to varying clutter levels in their foraging habitats. | 25,234,900 | [
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Loudness summation using focused and unfocused electrical stimulation. | With a cochlear implant, when stimulation from multiple channels is interleaved, the perceived loudness is greater than the loudness associated with any of the individual channels presented in isolation. This phenomenon is known as loudness summation. This study examined if loudness summation with monopolar and tripolar stimulation were equivalent at two loudnesses and two spacing configurations. Results suggest that loudness summation is similar for monopolar and tripolar modes. However, larger summation differences were observed for softer sounds and louder sounds with a larger spatial separation. The results are consistent with the idea that loudness summation is dependent on channel interaction and have implications for implementing current-focused processing strategies. | 25,234,912 | [
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Learning to discriminate frequency modulation rate can benefit and worsen pitch acuity. | Participants were trained to discriminate frequency modulation rates (FM-rate training) or Gabor patch orientations (visual training) in a same-different task for two different training lengths. Test discriminations involved trains of FM sweeps with identical modulation rates, but different frequencies. FM-rate training enhanced test accuracy (relative to visual) when sweep trains contained frequencies similar to training. For extended FM-rate training, the opposite was true for trains shifted one octave higher. In contrast to previous work, generalization of learning to the untrained dimension (pitch) was not well accounted for by conceptual learning. Mechanisms of stimulus learning may better explain the current cross-dimensional generalization. | 25,234,915 | [
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Non-classical nonlinear feature extraction from standard resonance vibration data for damage detection. | Dynamic non-classical nonlinear analyses show promise for improved damage diagnostics in materials that exhibit such structure at the mesoscale, such as concrete. In this study, nonlinear non-classical dynamic material behavior from standard vibration test data, using pristine and frost damaged cement mortar bar samples, is extracted and quantified. The procedure is robust and easy to apply. The results demonstrate that the extracted nonlinear non-classical parameters show expected sensitivity to internal damage and are more sensitive to changes owing to internal damage levels than standard linear vibration parameters. | 25,234,919 | [
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Access to care for adolescents seeking weight loss surgery. | Adolescents seeking weight loss surgery (WLS) frequently encounter obstacles obtaining treatment authorization from insurance carriers. This study identified factors influencing authorization for adolescents with clinical indications for WLS. A retrospective review was conducted for adolescents with clinical indications for WLS at five adolescent centers. This cohort represented a consecutive series of adolescents with insurance benefits for WLS for whom insurance authorization was sought between 2009 and 2011. Outcomes included number and timing of insurance authorizations for surgery, denials, and appeals. Records from 57 adolescents (74% female; mean age 16 (range: 12-17) years; mean BMI 51.3 kg/m(2) ) were reviewed. Of these, only 47% were approved with the original request. Eighty percent of those denied were approved on appeal, while 11% never obtained authorization for surgery. Age less than 18 years and proposed procedure were the most common reasons for denial. Less than half of adolescents with clinical indications for surgery received approval for the procedure on the first request. The appeal process typically resulted in overturning of denials, so that surgical care could be delivered. | 25,234,923 | [
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Pneumocystis pneumonia (PCP) and Pneumocystis jirovecii carriage in renal transplantation patients: a single-centre experience. | The Pneumocystis pneumonia is an increasing problem in transplanted patients: up to 25% suffer from Pneumocystis pneumonia, occurring during the first 6 months after transplantation. From 2001 to 2009, we investigated 21 patients with pneumonia after renal transplantation for the presence of Pneumocystis jirovecii. The laboratory diagnosis was established by Grocott and Giemsa staining methods and Pneumocystis-specific mitochondrial transcribed large subunit nested polymerase chain reaction (PCR). The PCR was also used for the differentiation of Pneumocystis pneumonia from Pneumocystis carriage. Of 21 patients, 7 had a Pneumocystis pneumonia, 6 were Pneumocystis carriers and 8 patients were negative. Four out of seven Pneumocystis pneumonia patients and two out of six patients with Pneumocystis carriage had a delayed graft function. An acute cytomegalovirus infection after transplantation was not detectable in the patients with Pneumocystis pneumonia, but in three patients with Pneumocystis carriage. Pneumocystis pneumonia was present in 33.3% of transplanted patients with suspected pneumonia. An association between acute rejection or co-infections and Pneumocystis pneumonia or carriage in patients after renal transplantation cannot be excluded. In three out of seven Pneumocystis pneumonia patients, an overlapping of hospitalisation times and an onset of Pneumocystis pneumonia 6 months after transplantation was found. Thus, person-to-person transmission seems probable in these cases. | 25,234,937 | [
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Histological evolution of pleuroparenchymal fibroelastosis. | To investigate the histological evolution in the development of pleuroparenchymal fibroelastosis (PPFE). We examined four patients who had undergone surgical lung biopsy twice, or who had undergone surgical lung biopsy and had been autopsied, and in whom the histological diagnosis of the first biopsy was not PPFE, but the diagnosis of the second biopsy or of the autopsy was PPFE. The histological patterns of the first biopsy were cellular and fibrotic interstitial pneumonia, cellular interstitial pneumonia (CIP) with organizing pneumonia, CIP with granulomas and acute lung injury in cases 1, 2, 3, and 4, respectively. Septal elastosis was already present in the non-specific interstitial pneumonia-like histology of case 1, but a few additional years were necessary to reach consolidated subpleural fibroelastosis. In case 3, subpleural fibroelastosis was already present in the first biopsy, but only to a small extent. Twelve years later, it was replaced by a long band of fibroelastosis. The septal inflammation and fibrosis and airspace organization observed in the first biopsies were replaced by less cellular subpleural fibroelastosis within 3-12 years. Interstitial inflammation or acute lung injury may be an initial step in the development of PPFE. | 25,234,959 | [
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A quasianalytical time domain solution for scattering from a homogeneous sphere. | A transient spherical multipole expansion-like solution for acoustic scattering from a spherical object is derived within a mesh-free and singularity-free time domain integral equation (TDIE) framework for the sound-soft, sound-rigid and penetrable cases. The method is based on an expansion of the time domain Green's function that allows independent evaluation of spatial and temporal convolutions. The TDIE system is solved by descretizing the integral equations in space and time, forming a matrix system via the method of moments, and solving the system with the marching on in time algorithm. Spatial discretization using tesseral harmonics leads to closed form expressions for spatial integrals, and use of a strictly band limited temporal interpolant permits efficient, accurate computation of temporal convolutions via numerical quadrature. The accuracy of these integrations ensures late time stability and accuracy of the deconvolution data. Results presented demonstrate the accuracy and convergence of the approach for broadband simulations compared with Fourier transformed analytical data. | 25,234,967 | [
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The origins of ambient biological sound from coral reef ecosystems in the Line Islands archipelago. | Although ambient biological underwater sound was first characterized more than 60 years ago, attributing specific components of ambient sound to their creators remains a challenge. Noise produced by snapping shrimp typically dominates the ambient spectra near tropical coasts, but significant unexplained spectral variation exists. Here, evidence is presented indicating that a discernible contribution to the ambient sound field over coral reef ecosystems in the Line Islands archipelago originates from the interaction of hard-shelled benthic macro-organisms with the coral substrate. Recordings show a broad spectral peak centered between 14.30 and 14.63 kHz, incoherently added to a noise floor typically associated with relatively "white" snapping shrimp sounds. A 4.6 to 6.2 dB increase of pressure spectral density level in the 11 to 17 kHz band occurs simultaneously with an increase in benthic invertebrate activity at night, quantified through time-lapse underwater photography. Spectral-level-filtered recordings of hermit crabs Clibanarius diugeti in quiet aquarium conditions reveal that transient sounds produced by the interaction between the crustaceans' carapace, shell, and coral substrate are spectrally consistent with Line Islands recordings. Coral reef ecosystems are highly interconnected and subtle yet important ecological changes may be detected quantitatively through passive monitoring that utilizes the acoustic byproducts of biological activity. | 25,234,977 | [
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Influence and interactions of laryngeal adductors and cricothyroid muscles on fundamental frequency and glottal posture control. | The interactions of the intrinsic laryngeal muscles (ILMs) in controlling fundamental frequency (F0) and glottal posture remain unclear. In an in vivo canine model, three sets of intrinsic laryngeal muscles-the thyroarytenoid (TA), cricothyroid (CT), and lateral cricoarytenoid plus interarytenoid (LCA/IA) muscle complex-were independently and accurately stimulated in a graded manner using distal laryngeal nerve stimulation. Graded neuromuscular stimulation was used to independently activate these paired intrinsic laryngeal muscles over a range from threshold to maximal activation, to produce 320 distinct laryngeal phonatory postures. At phonation onset these activation conditions were evaluated in terms of their vocal fold strain, glottal width at the vocal processes, fundamental frequency (F0), subglottic pressure, and airflow. F0 ranged from 69 to 772 Hz and clustered into chest-like and falsetto-like groups. CT activation was always required to raise F0, but could also lower F0 at low TA and LCA/IA activation levels. Increasing TA activation first increased then decreased F0 in all CT and LCA/IA activation conditions. Increasing TA activation also facilitated production of high F0 at a lower onset pressure. Independent control of membranous (TA) and cartilaginous (LCA/IA) glottal closure enabled multiple pathways for F0 control via changes in glottal posture. | 25,235,003 | [
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Direct generation of 2-ps blue pulses from gain-switched InGaN VCSEL assessed by up-conversion technique. | Ultra-short pulses in blue region generated from compact and low-cost semiconductor lasers have attracted much attention for a wide variety of applications. Nitride-based vertical-cavity surface-emitting lasers (VCSELs), having intrinsic high material gain and short cavities, favor the generation of ultra-short blue pulses via a simple gain-switching technique. In this study, we fabricated a single-mode InGaN VCSEL consisting of 10-period InGaN/GaN quantum wells (QWs). The output pulses were evaluated accurately with an up-conversion measurement system having time resolution of 0.12 ps. We demonstrated that ultra-short blue pulses, as short as 2.2 ps at 3.4 K and 4.0 ps at room temperature, were generated from the gain-switched InGaN VCSEL via impulsive optical pumping, without any post-processing. The gain-switched pulses we obtained should greatly promote the development of ultra-short blue pulse generation. In addition, this successful assessment demonstrates the up-conversion technique's usefulness for characterizing ultra-short blue pulses from semiconductor lasers. | 25,236,162 | [
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Halopyrroles: a new group of highly toxic disinfection byproducts formed in chlorinated saline wastewater. | Utilizing seawater for toilet flushing is an effective way to conserve freshwater in coastal cities. During chlorination for disinfecting saline wastewater effluents, the high levels of bromide from seawater are oxidized to hypobromous acid which may then react with effluent organics to form brominated disinfection byproducts (DBPs). In this research, by applying a new precursor ion scan method, we detected and identified a group of halopyrroles in a chlorinated saline wastewater effluent, including tetrabromopyrrole, tribromochloropyrrole, tribromoiodopyrrole, and tribromopyrrole, with tetrabromopyrrole as the predominant species. It is the first time that this group of halopyrroles were identified as wastewater DBPs (though 2,3,5-tribromopyrrole has been found to be a DBP in drinking water before). Detection of halopyrroles was problematic as these compounds in the pretreated samples were found to convert to halonitropyrroles; the problem was successfully solved by diluting the pretreated samples. The formation, occurrence, precursor, and toxicity of tetrabromopyrrole were investigated. This DBP showed significantly higher developmental toxicity than any of the haloaliphatic and haloaromatic DBPs previously tested. | 25,236,171 | [
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Quo vadis: advanced prostate cancer-clinical care and clinical research in the era of multiple androgen receptor-directed therapies. | The novel androgen receptor-directed therapies abiraterone acetate and enzalutamide, having demonstrated improved survival in randomized phase 3 studies of men with metastatic castration-resistant prostate cancer, have ushered in a new era in the treatment of this disease. Additional novel androgen receptor-directed therapies, such as ARN-509 and orteronel, are in various phases of clinical trials and development. However, the emergence of therapeutic resistance and clinical disease progression is inevitable. Although advances in genomic technologies have led to unprecedented understanding of the biology of castration-resistant prostate cancer, efforts only now are underway to elucidate the mechanisms of resistance associated with abiraterone and enzalutamide. A tremendous challenge in the near future will be to determine the optimal sequence or combination of therapies to overcome resistance mechanisms. In this review, the current landscape of androgen receptor-directed therapies and future directions necessary to enhance their clinical efficacy for the maximal benefit of patients are discussed. | 25,236,176 | [
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Ablation of focal atrial tachycardia from the non-coronary aortic cusp: case series and review of the literature. | Focal atrial tachycardia successfully ablated from the non-coronary cusp (NCC) is rare. Our aim was to describe the characteristics of mapping and ablation therapy of NCC focal atrial tachycardias and to provide a comprehensive review of the literature. Seven patients (age 40 ± 9 years) with symptomatic, drug-refractory atrial tachycardia were referred for electrophysiological study. Extensive right and left atrial mapping revealed atrial tachycardia near His in all patients but either failed to identify a successful ablation site or radiofrequency applications only resulted in temporary termination of the tachycardia. Mapping and ablation of the NCC were performed retrogradely via the right femoral artery. Mapping of the NCC demonstrated earliest atrial activation during atrial tachycardia 38 ± 14 ms (ranging 17-56 ms) before the onset of the P-wave. Earliest atrial activation in the NCC was earlier than earliest activation in the right atrium and left atrium in all patients. The P-wave morphology was predominantly negative in the inferior leads and biphasic in leads V1 and V2. The tachycardia was successfully terminated by radiofrequency application in 10 ± 6 s (2-16 s), without complications. All patients were free of symptoms during a follow-up of 19 ± 9 months. Literature search revealed 18 reports (91 patients) describing NCC focal atrial tachycardia, with 99% long-term ablation success with a 1% complication rate. Symptomatic focal atrial tachycardia near His may originate from the NCC and can be treated safely and effectively with radiofrequency ablation. | 25,236,180 | [
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Data calibration and reduction allows to visualize behavioural profiles of psychosocial influences in mice towards clinical domains. | Psychosocial stress-particularly in combination with genetic vulnerability-is a critical environmental risk factor for psychiatric diseases in humans. Isolation rearing (IR) and social defeat (SD) paradigms model psychosocial risk factors in rodents, while enriched environment (EE) protects them from behavioural deficits. Studying the influence of various environmental conditions, e.g., on genetic mouse models can help to dissect the complex gene-environment relationships underlying human psychiatric diseases. Such studies may require analysing multiple mouse cohorts; however, the comparability of behavioural experiments is challenging and often compromised by practical limitations such as group sizes and influences of handling. Therefore, protocol standardization as well as appropriate statistical normalization is necessary to compare different experiments. In this study, we analysed two independent cohorts to compare the behavioural profiles of wild-type male mice subjected to IR and SD. In both cases, EE conditions served as a reference. Multivariate statistics was applied to merge the data from individual measures into broader categories (such as curiosity, anxiety and fear memory) by estimating their calibrated joint effect within a category. Plotting and overlaying these calibrated effect sizes in a single graph allowed intuitive comparison of IR and SD behavioural profiles. This approach allows analysing multiple behavioural tests at once, which is more relevant to psychiatric syndromes than focusing on single behavioural measures. Our method revealed that motivation and fear memory are impaired by both conditions, whereas ambulation and pain sensitivity are affected only by IR and curiosity is mainly diminished upon SD. Thus, IR could be a paradigm of choice in studies focusing on positive symptoms, while SD might be more relevant for negative and cognitive symptoms. | 25,236,183 | [
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A pharmaceutical industry perspective on the economics of treatments for alcohol and opioid use disorders. | Individuals with alcohol and/or drug use disorders often fail to receive care, or evidence-based care, yet the literature shows health economic benefits. Comparative effectiveness research is emerging that examines approved approaches in terms of real, total healthcare cost/utilization. Comprehensive retrospective insurance claims analyses are few but tend to be nationally distributed and large. The emerging pattern is that, while treatment in general is cost effective, specific therapeutics can yield different health economic outcomes. Cost/utilization data consistently show greater savings with pharmacotherapies (despite their costs) versus psychosocial treatment alone. All FDA-approved addiction pharmacotherapies (oral naltrexone, extended-release naltrexone, acamprosate, disulfiram, buprenorphine, buprenorphine/naloxone, and methadone) are intended for use in conjunction with psychosocial management, not as stand-alone therapeutics; hence, pharmacotherapy costs must offer benefits in addition to abstinence alone or psychological therapy. Patient persistence is problematic, and (despite its cost) extended-release pharmacotherapy may be associated with lower or no greater total healthcare cost, mostly due to reduced hospitalization. The reviewed studies use rigorous case-mix adjustment to balance treatment cohorts but lack the randomization that clinical trials use to protect against confounding. Unlike trials, however, these studies can offer generalizability to diverse populations, providers, and payment models--and are of particular salience to payers. | 25,236,185 | [
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Asparagine in plums detected by CEST-MRI. | Magnetic resonance imaging (MRI) relies on the topological distribution of the intense water NMR signal and may be used to report about changes in the internal structures of fruits associated to ripening, storing, pathogen infection. Herein the use of CEST-MRI (chemical exchange saturation transfer) is introduced to show that in addition to structural information, insights into the presence in the fruits of specific chemicals may be gained. Asparagine is present in plums at relatively high concentration (≈10-20mM) and owns two amide protons (at 2.1 and 2.8ppm down field from water) in slow exchange with water protons. By irradiating the amide resonances with a proper rf-field it is possible to transfer saturated magnetization to the "bulk" water signal. The attained change in signal intensity reflects the extent of prototropic exchange between amide and water protons that is modulated by the local pH. | 25,236,190 | [
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Chemical and sensory comparison of fresh and dried lulo (Solanum quitoense Lam.) fruit aroma. | The odour-active volatile compounds of lulo fruit (Solanum quitoense Lam.) were isolated by solvent extraction followed by solvent-assisted flavour evaporation (SAFE). GC-O and GCMS analyses as well as quantitation by internal standard method showed that (Z)-3-hexenal, ethyl butanoate, 3-sulphanylhexyl acetate, and ethyl hexanoate were key aroma compounds in this fruit. Other odorants with relevance because their contribution (high OAVs) to the overall aroma were 4-hydroxy-2,5-dimethyl-3(2H)-furanone, methyl benzoate, (E)-2-hexenal, and hexanal. Lulo fruit pulp in presence of maltodextrin DE-20 was dried by using four different types of drying methods: hot air-drying (HD), spray drying (SD), lyophilisation (LD), and ultrasonic convective hot air-drying (HUD). LD sample exhibited the highest sensory rank (lulo-like) in comparison with fresh fruit pulp. Hot-air drying processes (HD and HUD) changed adversely the aroma of lulo fruit pulp. | 25,236,202 | [
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Variability in chemical composition of Vitis vinifera cv Mencía from different geographic areas and vintages in Ribeira Sacra (NW Spain). | A chemical study was conducted from 2009 to 2012 to examine spatial and seasonal variability of red Vitis vinifera Mencía located in different geographic areas (Amandi, Chantada, Quiroga-Bibei, Ribeiras do Sil and Ribeiras do Miño) from NW Spain. Mencía samples were analysed for phenolic, (flavan-3-ols, flavonols, anthocyanins, acids and resveratrol), nitrogen (TAC, TAN, YAN and TAS) and volatiles compounds (alcohols, C6 compounds, ethyl esters, terpenes, aldehydes, acids, lactones, volatile phenols and carbonyl compounds) by GC-MS and HPLC. Results showed that the composition of Mencía cultivar was more affected by the vintage than the geographic area. The amino acid composition was less affected by both geographic origin and vintage, showing more varietal stability. Application of Principal Component Analysis (PCA) to experimental data showed a good separation of Mencía grape according to geographical origin and vintages. PCA also showed high correlations between the ripening ratio and C6 compounds, resveratrol and carbonyl compounds. | 25,236,215 | [
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Application of FTIR-ATR spectroscopy to the quantification of sugar in honey. | A Fourier transform infrared spectroscopic method with attenuated total reflectance (FTIR-ATR) and partial least squares (PLS) regression model for the prediction of sugar content in honey samples was calculated. Standards of trehalose, glucose, fructose, sucrose, melezitose, turanose and maltose were used to identify and quantify the individual sugar components in 63 honey samples by HPAEC-IPAD. Fructose and glucose are the highest sugars in honey with an average value of 36% and 26%, respectively. The 1stDer spectra with MSC or SLS in the wave number range from 1500 to 750cm(-1) provide the best calibration model with a r(2) of 86.60 and 86.01 with RPD of 2.6 and 2.55, respectively for fructose and glucose. For turanose and melezitose good models were also found. The FTIR-ATR showed to be a good methodology to quantify the main sugar content in honey and easily adapted to routine analysis. | 25,236,219 | [
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Separation and determination of 4-methylimidazole, 2-methylimidazole and 5-hydroxymethylfurfural in beverages by amino trap column coupled with pulsed amperometric detection. | A method for simultaneous determination of 4-methylimidazole (4-MeI), 2-methylimidazole (2-MeI) and 5-hydroxymethylfurfural (HMF) in beverages was developed using solid-phase extraction (SPE) and amino trap column coupled with pulsed amperometric detection (AMTC-PAD). A single amino trap column (P/N: 046122) was first applied to separate the targeted analytes in samples after SPE pretreatment. This method demonstrated low limit of quantification (0.030mg/L for methylimidazoles and 0.300mg/L for HMF) and excellent linearity with correlation of determination (R(2)=0.999 for 2-MeI, 0.997 for 4-MeI and 0.998 for HMF). Nearly no 2-MeI was found in all soft drinks. However, 4-MeI could be detected in cola drinks and soft drinks containing caramel colour (ranging from 0.13 to 0.34mg/L), whereas HMF were only found in cola drinks (ranging from 1.07 to 4.47mg/L). Thus, AMTC-PAD technique would be a valid and inexpensive alternative to analysis of 4-MeI, 2-MeI and HMF. | 25,236,220 | [
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Effects of postharvest curing treatment on flesh colour and phenolic metabolism in fresh-cut potato products. | The flesh colour and phenolic metabolism in potato tuber during curing and after cut were investigated. Result indicated that postharvest curing not only changed phenolic metabolism during curing, but also improved fresh-cut colour for 12 days after fresh cut. Significantly lower PAL and higher phenolic content and PPO activities during curing treatment and fresh-cut potatoes were detected compared to the control, which lead to the lower browning in the slices from curing treated potatoes. HPLC analysis revealed that amounts of total phenolics, chlorogenic acid, gallic acid and protocatechuic acid were induced by curing and highly accumulated in the curing treated potatoes. Our results demonstrated that phenolic metabolism played an important role in the control of browning of fresh cut potato after curing. | 25,236,223 | [
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A multiplex real-time PCR method for the quantification of beef and pork fractions in minced meat. | One popular staple food in many lands is minced meat, traditionally prepared from beef and/or pork fractions. While beef is the more expensive of the two meat fractions, the possibility exists for manufacturers to fraudulently declare higher proportions of it. Additionally, the need exists to protect consumers who, out of medical or ethical reasons, reject specific meat fractions. In this work, we report on a quantitative triplex real-time PCR approach for the quantification of meat in minced meat products. With the method, beef and pork fractions are quantified employing primer and probe sequences that specifically recognise cow and pig components, against the backdrop of myostatin, a universal sequence commonly found in mammals and poultry species. The limit of detection of the qPCR method was 20 genome equivalents, while the measurement of uncertainty was determined at 1.83%. The method was validated on several commercially available minced meat products and performed well in terms of handling, reproducibility and robustness. | 25,236,231 | [
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Enzymatic synthesis of 3-O-α-maltosyl-l-ascorbate using an engineered cyclodextrin glucanotransferase. | A mutant derived from a cyclodextrin glucantransferase with an alanine residue as its acid/base catalyst residue (CGT-E284A) catalyzed regioselective glycosylation at 3-OH of l-ascorbic acid using α-maltosyl fluoride (αG2F) and l-ascorbic acid as the donor and acceptor, respectively, yielding 3-O-α-maltosyl-l-ascorbate (AA3αG2). The optimum conditions were determined by high-performance liquid chromatography analysis with 20mM αG2F and 40mM l-ascorbic acid as the substrates at pH 7.5 and 25°C with 1mg/ml of the enzyme for 24h. Calcium ions bound in CGT-E284A played an important role in the transglycosylation. CGT-E284A exhibited typical saturation kinetic behaviour for αG2F at a fixed acceptor concentration (40mM), and substrate inhibition by l-ascorbic acid was observed at high l-ascorbic acid concentrations (>60mM). AA3αG2 was isolated from a preparative scale reaction with a yield of 29%, and it showed extremely high stability under oxidative conditions. | 25,236,239 | [
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White tea (Camellia sinensis) inhibits proliferation of the colon cancer cell line, HT-29, activates caspases and protects DNA of normal cells against oxidative damage. | Tea (Camellia sinensis) is one of the most consumed beverages in the world. White tea is made from the buds and young leaves of the tea plant which are steamed and dried, whilst undergoing minimal oxidation. The MTT assay was used to test the extract on the effect of the proliferation of the colorectal cancer cell line, HT-29. The extract inhibited the proliferation of HT-29 cells with an IC50 of 87μg/ml. The extract increased the levels of caspase-3, -8, and -9 activity in the cells. DNA damage in 3T3-L1 normal cells was detected by using the comet assay. The extract protected 3T3-L1 cells against H2O2-induced DNA damage. The results from this study show that white tea has antioxidant and antiproliferative effects against cancer cells, but protect normal cells against DNA damage. Regular intake of white tea can help to maintain good health and protect the body against disease. | 25,236,244 | [
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Gonad-infecting species of Philometra (Nematoda: Philometridae) from groupers Epinephelus spp. (Osteichthyes: Serranidae) in the Bay of Bengal, India. | Based on light and scanning electron microscopical studies, two new and one specifically not identified gonad-infecting species of Philometra Costa, 1845 (Nematoda: Philometridae) are described from the ovary of marine fishes of the genus Epinephelus Bloch (Serranidae, Perciformes) in the Bay of Bengal, off the eastern coast of India: P. indica sp. nov. (male and females) from the honeycomb grouper E. merra Bloch, P. tropica sp. nov. (males and females) from the duskytail grouper E. bleekeri (Vaillant) and Philometra sp. (only females) from the cloudy grouper E. erythrurus (Valenciennes). Philometra indica is mainly characterized by the length of spicules 192-195 μm and the gubernaculum 84 μm, the distal tip of the gubernaculum without a dorsal protuberance, and by the presence of five pairs of caudal papillae. Philometra tropica is mainly characterized by the spicules conspicuously ventrally distended at their posterior halves, the distal tip of the gubernaculum with a dorsal protuberance, and the presence of three pairs of caudal papillae. | 25,236,267 | [
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A new species of Cacatuocotyle (Monogenea, Dactylogyridae) parasitizing two species of Astyanax (Ostariophysi, Characidae) in southern Brazil. | A new species of Cacatuocotyle is described from the external surface of Astyanax aff. fasciatus and Astyanax jacuhiensis from Lake Guaíba, State of Rio Grande do Sul, Brazil. It differs from the other three species of the genus, recorded from Mexico and the State of Paraná, Brazil, by possessing an accessory piece with a long proximal portion, a U-shaped bar with irregular posterior margin in its midportion, and a haptor containing two circular thickenings with muscular anterior margins. Only one monogenean species, Urocleidoides astyanacis (= Characithecium costaricensis) was recorded for the host Astyanax aff. fasciatus, whereas none were known for A. jacuhiensis. This paper records a new host (A. jacuhiensis) for monogeneans in southern Brazil and extends southward with the geographical distribution of the genus Cacatuocotyle to the State of Rio Grande do Sul, Brazil. | 25,236,274 | [
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The first clinically manifested case of angiostrongylosis in a dog in Slovakia. | The first clinical case of canine angiostrongylosis from Slovakia, previously infection-free country, is described. 18-month old male Bernese mountain dog living in south-eastern part of Slovakia showed poor health condition characterized by weight loss, irritating cough, dispnoe, intense salivation, vomiting and bilateral scleral bleeding. Two times even the acute physical collapse occurred. Blood analysis was provided and revealed increase of total protein, eosinophilia, monocytosis, and mild thrombocytopenia. Anaemia characterized by reduced number of erythrocytes and reduced levels of haemoglobin, packed cell volume and iron was also diagnosed. Larvoscopic Baermann technique revealed the presence of Angiostrongylus first stage larvae. Infected dog excreted larvae in high numbers - in 10 g of the faecal material more than 800 larvae were counted. DNA analysis using PCR confirmed the presence of Angiostrongylus vasorum species. The first clinical case of angiostrongylosis has evidenced that the new life-threatening parasitic disease of dogs has spread to the territory of Slovakia. A serious effort is therefore inevitable to increase the professional awareness and knowledge on diagnosis, treatment and prevention. | 25,236,277 | [
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On a new species of Aplectana (Nematoda, Cosmocercidae) from Kulti, Burdwan, West Bengal, India. | During routine survey for amphibian nematodes from coalfield areas of West Bengal, India 7 male and 12 female nematodes were recovered from the rectum of one out of three Duttaphrynus melanostictus (Schneider, 1899) examined for helminth infection from Kulti, Burdwan. On examination the recovered nematodes were found to belong to a new species of the genus Aplectana (Nematoda: Cosmocercidae) and the name Aplectana duttaphryni sp. nov. is proposed for them. This species is most similar to those species which possess gubernaculum but differs from all by distribution pattern of caudal papillae. Aplectana duttaphryni sp. nov. represents 49(th) species assigned to the genus, but only the 4(th) species reported from Oriental realm and second from India. | 25,236,282 | [
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Understanding medication oversupply and its predictors in the outpatient departments in Thailand. | Medication oversupply is an important problem in the healthcare systems. It causes unnecessary avoidable healthcare costs. Although some studies have determined the magnitude and financial loss due to medication oversupply in western countries, they may not be applicable to Asia-pacific countries. This study aims to determine the prevalence, financial loss, and patterns of medication oversupply and the factors associated with such oversupply in Thailand. A retrospective database analysis was used from 3 public hospitals. Patients visiting the outpatient department of the hospitals in 2010 and receiving at least 2 prescriptions within 6 months were included. The modified medication possession ratio (MPRm) was used to determine the medication supply. Patients having MPRm > 1.20 were defined as receiving a medication oversupply. The measures were prevalence of medication oversupply, the number of oversupplied medications, and financial loss (2012 dollars) due to medication oversupply. Hierarchical logistic regression was used to determine the factors associated with the prevalence of medication oversupply. A total of 99,743 patients were included. Patients were on average 49.7 ± 21.2 years of age, and 42.8% were male. Most of them were adult (53.7%). Among those patients, 60.2% of the patients were under universal coverage schemes. Around 13.4% of all the patients received a medication oversupply, and the patients in regional hospitals had a higher prevalence of medication oversupply than patients in district hospitals (13.8% VS 8.2%). The patients under civil servant medical benefit schemes (CSMBS) (13.6%) had the most prevalence of medication oversupply. The total financial loss was $189,024 per year. The average financial loss was $1.9 ± 19.0 per patient/year. Patients under CSMBS experienced the highest average financial loss (2.6 ± 23.2 $/patient/year). Age, gender, health insurance schemes, and the number of medications that the patients received were the factors associated with medication oversupply. Medication oversupply is an important problem for the health system. Patients receiving care from regional hospitals had a higher likelihood of medication oversupply. Policymakers may consider developing policies for preventing medication oversupply. The policy should be implemented in regional hospitals and especially in children or patients with poly-pharmacy. | 25,236,345 | [
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An investigation of factors that impact patients' subjective experience of nurse-led clinics: a qualitative systematic review. | To systematically review the qualitative evidence on factors that affect the experience of patients attending nurse-led clinics and compare with key elements of person-centred care. As the number of nurse-led clinics increases in response to health system needs, evaluation has focused on clinical outcomes and cost. Patient experiences are less researched and yet, they are an important influence on clinical outcomes and an indicator of person-centred care. A detailed review of existing research in this area is needed. A systematic review of primary, qualitative literature was conducted using the Joanna Briggs Institute methodology of meta-aggregation. Published research from 1990-2012 was located using CINAHL, PubMed, Medline and PsycINFO. Reference lists were searched and analysed. Two reviewers assessed the papers for methodological quality using instruments from the Joanna Briggs Institute to critically appraise, extract data and meta-aggregate findings. Eleven studies met all inclusion criteria. Three meta-synthesis statements were derived from 46 findings aggregated to nine categories. The key themes relating to establishment of a therapeutic relationship, effective communication, and clinical skills and collaboration mapped closely to the person-centred care framework. Concepts central to person-centred care proved to be factors impacting patients' subjective experience. Further research is warranted to meet the challenge to transform the key concepts of the person-centred care model into everyday nursing practice. Knowledge of patients' feelings and the importance of person-centred, individualised care may contribute to development of future training and re-training programs in basic nursing skills. This is significant in that it contributes to future positive patient experience. | 25,236,376 | [
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Is magnetite a universal memory molecule? | Human stem cells possess memory, and consequently all living human cells must have a memory system. How memory is stored in cells and organisms is an open question. Magnetite is perhaps the best candidate to be a universal memory molecule. Magnetite may give us a clue, because it is the Earth's most distributed and important magnetic material. It is found in living organisms with no known functions except for involvement in navigation in some organisms. In humans magnetite is found in the brain, heart, liver and spleen. Humans suffer from memory dysfunctions in many cases when iron is out of balance. Anomalous concentrations of magnetite is known to be associated with a neurodegenerative disorder like Alzheimer's disease. Due to the rapid speed and accuracy of our brain, memory and its functions must be governed by quantum mechanics. | 25,236,401 | [
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Effects of the administration of epidermal growth factor receptor specific inhibitor cetuximab, alone and in combination with cisplatin, on proliferation and apoptosis of Hep-2 laryngeal cancer cells. | Epidermal growth factor receptor (EGFR) overexpression and prognostic value in head and neck squamous cell cancer is the basis for targeting by anti-EGFR antibodies, which increase the efficacy of radiotherapy. In order to evaluate the best therapeutic schedule, the effects of cetuximab (C225) on Hep-2 cell proliferation, alone and in combination with cisplatin, were studied. Hep-2 cells were treated with cetuximab alone or in combination with cisplatin. After determining cell viability with trypan blue, morphological features of apoptotic degeneration were analysed by fluorescence microscopy with Hoechst 33258 stain. Cetuximab alone mildly inhibited Hep-2 proliferation and showed no pro-apoptotic effects. When administered concomitantly with cisplatin, cetuximab synergistically increased inhibition of proliferation and apoptosis. The antiproliferative activity of cetuximab is consistent with its hypothesised role in inhibiting repopulation. However, the increase in the effects of pro-apoptotic agents induced by cetuximab may be even more relevant to its clinical effectiveness than the inhibition of repopulation. | 25,236,402 | [
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Differential stress response in rats subjected to chronic mild stress is accompanied by changes in CRH-family gene expression at the pituitary level. | The purpose of this study was to examine molecular markers of the stress response at the pituitary and peripheral levels in animals that responded differently to chronic mild stress (CMS). Rats were subjected to 2-weeks CMS and symptoms of anhedonia was measured by the consumption of 1% sucrose solution. mRNA levels of CRH-family neuropeptides (Crh-corticotropin-releasing hormone, Ucn1-urocortin 1, Ucn2-urocortin 2, Ucn3-urocortin 3), CRH receptors (Crhr1-corticotropin-releasing hormone receptor 1, Crhr2-corticotropin-releasing hormone receptor 2) and Crhbp (corticotropin-releasing factor binding protein) in the pituitaries of rats were determined with real-time PCR. Plasma levels of ACTH (adrenocorticotropin), CRH and urocortins were measured with ELISA assays. CMS procedure led to the development of anhedonia manifested by the decreased sucrose consumption (stress-reactive, SR, stress-susceptible group). Additionally, the group of animals not exhibiting any signs of anhedonia (stress non-reactive, SNR, stress-resilient group) and the group characterized by the increased sucrose consumption (stress invert-reactive group SIR) were selected. The significant increases in ACTH plasma level accompanied by the decreases in the pituitary gene expression of the Crh, Ucn2 and Ucn3 in both stress non-reactive and stress invert-reactive groups were observed. The only molecular change observed in stress-reactive group was the increase in UCN2 plasma level. The differentiated behavioral stress responses were reflected by gene expression changes in the pituitary. Alterations in the mRNA levels of Crh, Ucn2 and Ucn3 in the pituitary might confirm the paracrine and/or autocrine effects of these peptides in stress response. The opposite behavioral effect between SNR vs. SIR groups and the surprising similarity at gene expression and plasma ACTH levels in these two groups may suggest the discrepancy between molecular and behavioral stress responses; however, there results might indicate to similarity underlying different ways to cope with stress conditions. | 25,236,411 | [
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Global evolution of Equidae and Gomphotheriidae from South America. | The contemporary South American mammalian communities were determined by the emergence of the Isthmus of Panama and by the profound climatic oscillations during the Pleistocene. Horses and gomphotheres were 2 very conspicuous groups of immigrant mammals from North America that arrived in South America during the Pleistocene. The present study compiles updated data on the phylogeny, systematics and ecology of both groups in South America. The horses in South America are represented by 2 genera, Hippidion and Equus, as are the gomphotheres, represented by Cuvieronius and Stegomastodon. Both genera of horses include small (Hippidion devillei, H. saldiasi, E. andium and E. insulatus) and large forms (Equus neogeus and H. principale), which dispersed into South America using 2 different routes. The possible model for this dispersion indicates that the small forms used the Andes corridor, while larger horses dispersed through the eastern route and through some coastal areas. In the case of gomphotheres, Cuvieronius and Stegomastodon reached South America in 2 independent dispersal events, and Cuvieronius dispersed across the Andean corridor, while large Stegomastodon spread along the eastern route. Horses and gomphotheres present values of δ(13) C from woodlands to C4 grasslands. Hippidion present lower values of δ(13) C than Equus in the late Pleistocene, whereas the gomphotheres diverge from value of δ(18) O, reflecting that Cuvieronius inhabited the Andean corridor and Stegomastodon dispersed through eastern plains. The gomphothere and horse species recorded in South America became extinct around the time that humans arrived. | 25,236,414 | [
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A multifunctional 3D chiral porous ferroelectric metal-organic framework for sensing small organic molecules and dye uptake. | A flexible aromatic multicarboxylate ligand and Cd(II) ions assemble into a chiral multihelical porous metal-organic framework with second-order nonlinear optical and ferroelectric properties. The obtained guest-free form highly selectively senses small organic molecules and adsorbs large dye molecules. | 25,236,428 | [
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Expression pattern of neuronal intermediate filament α-internexin in anterior pituitary gland and related tumors. | α-Internexin (INA) is a class IV neuronal intermediate filament protein that maintains the morphogenesis of neurons. It is expressed in developing neuroblasts and represents the major component of the cytoskeleton in cerebellar granule cells of adult central nervous system tissue. Data concerning INA expression in the human frontal pituitary lobe and related adenomas (PA) is missing. Using immunohistochemistry we examined the distribution pattern of INA in a large cohort of 152 PA, 11 atypical PA, 4 pituitary carcinomas and 20 normal pituitaries (overall n = 187). Quantity of INA protein expression was semi-quantitatively evaluated and grouped into five categories (0 = 0%; 1 = >0-5%; 2 = >5-35%; 3 = >35-80%; 4 = >80% of cells). Cellular staining intensity of INA appeared significantly higher in gonadotropinomas (Go, n = 62), null cell adenomas (NC, n = 7) and thyrotropinomas (TSHomas, n = 7) compared to the other tumor subtypes (p ≤ 0.001). Furthermore, Go and NC showed a peculiar pseudorosette-like staining pattern surrounding blood vessels in 85.5% (59/69) of cases. Interestingly, areas exhibiting homogenous INA staining were often associated with oncocytic cell changes and decreased immunohistochemically detectable hormone expression. Only 8.5% (8/94) of other PA showed a comparable INA distribution (p ≤ 0.001). Go, NC as well as TSHomas exhibit high levels of intracellular INA protein indicating neuronal transdifferentiation. A possible impact on pathogenesis and endocrine activity needs further investigation. | 25,236,435 | [
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Development of a Chronic Care Model for Neurological Conditions (CCM-NC). | Persons with neurological conditions and their families face a number of challenges with the provision of health and community-based services. The purpose of this study was to understand the existing health and community service needs and gaps in care and to use this information to develop a model to specify factors and processes that may improve the quality of care and health and well-being for persons with neurological conditions. We conducted semi-structured interviews with health care professionals, community-based non-health care professionals working with individuals with neurological conditions, and policy makers -from the Ministries of Health, Community and Social Services, Transportation and Education- across Canada. We used a purposive sampling and snowballing approach to obtain maximum variation across professions, sector and geography (provinces and territories, rural and urban). Data analysis was an iterative, constant comparative process involving descriptive and interpretive analyses and was initially guided by the components of the Expanded Chronic Care Model. A total of 180 individuals completed the interviews: 39% (n = 70) health care professionals, 47% (n = 85) community-based non-health care professionals, and 14% (n = 25) policy makers. Based on the data we developed the Chronic Care Model for Neurological Conditions (CCM-NC). The major needs/gaps are represented by the following themes: acceptance and openness to neurological conditions, evidence informed policy, investments and funding, supported transitions, caregiver support, and life enhancing resources (education, employment, housing and transportation), knowledge and awareness of neurological conditions and availability and access to health services. The model maintains that intersectoral collaboration across the health system, community and policy components is needed. It recognizes that attitudes, policies, enhanced community integration and health system changes are needed to develop activated patients and families, proactive service delivery teams, a person-centred health system and healthy public policy for persons with neurological conditions. The CCM-NC will generate debate and discussion about the actions needed in each of the model components to enable people with neurological conditions to sustain healthier lives. Next steps include validating the model with persons with neurological conditions, in and outside of the Canadian context and developing and evaluating interventions to test the model. | 25,236,443 | [
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Fine-mapping nicotine resistance loci in Drosophila using a multiparent advanced generation inter-cross population. | Animals in nature are frequently challenged by toxic compounds, from those that occur naturally in plants as a defense against herbivory, to pesticides used to protect crops. On exposure to such xenobiotic substances, animals mount a transcriptional response, generating detoxification enzymes and transporters that metabolize and remove the toxin. Genetic variation in this response can lead to variation in the susceptibility of different genotypes to the toxic effects of a given xenobiotic. Here we use Drosophila melanogaster to dissect the genetic basis of larval resistance to nicotine, a common plant defense chemical and widely used addictive drug in humans. We identified quantitative trait loci (QTL) for the trait using the DSPR (Drosophila Synthetic Population Resource), a panel of multiparental advanced intercross lines. Mapped QTL collectively explain 68.4% of the broad-sense heritability for nicotine resistance. The two largest-effect loci-contributing 50.3 and 8.5% to the genetic variation-map to short regions encompassing members of classic detoxification gene families. The largest QTL resides over a cluster of ten UDP-glucuronosyltransferase (UGT) genes, while the next largest QTL harbors a pair of cytochrome P450 genes. Using RNAseq we measured gene expression in a pair of DSPR founders predicted to harbor different alleles at both QTL and showed that Ugt86Dd, Cyp28d1, and Cyp28d2 had significantly higher expression in the founder carrying the allele conferring greater resistance. These genes are very strong candidates to harbor causative, regulatory polymorphisms that explain a large fraction of the genetic variation in larval nicotine resistance in the DSPR. | 25,236,448 | [
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High-resolution genetic mapping of complex traits from a combined analysis of F2 and advanced intercross mice. | Genetic influences on anxiety disorders are well documented; however, the specific genes underlying these disorders remain largely unknown. To identify quantitative trait loci (QTL) for conditioned fear and open field behavior, we used an F2 intercross (n = 490) and a 34th-generation advanced intercross line (AIL) (n = 687) from the LG/J and SM/J inbred mouse strains. The F2 provided strong support for several QTL, but within wide chromosomal regions. The AIL yielded much narrower QTL, but the results were less statistically significant, despite the larger number of mice. Simultaneous analysis of the F2 and AIL provided strong support for QTL and within much narrower regions. We used a linear mixed-model approach, implemented in the program QTLRel, to correct for possible confounding due to familial relatedness. Because we recorded the full pedigree, we were able to empirically compare two ways of accounting for relatedness: using the pedigree to estimate kinship coefficients and using genetic marker estimates of "realized relatedness." QTL mapping using the marker-based estimates yielded more support for QTL, but only when we excluded the chromosome being scanned from the marker-based relatedness estimates. We used a forward model selection procedure to assess evidence for multiple QTL on the same chromosome. Overall, we identified 12 significant loci for behaviors in the open field and 12 significant loci for conditioned fear behaviors. Our approach implements multiple advances to integrated analysis of F2 and AILs that provide both power and precision, while maintaining the advantages of using only two inbred strains to map QTL. | 25,236,452 | [
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Bayesian modeling of haplotype effects in multiparent populations. | A general Bayesian model, Diploffect, is described for estimating the effects of founder haplotypes at quantitative trait loci (QTL) detected in multiparental genetic populations; such populations include the Collaborative Cross (CC), Heterogeneous Socks (HS), and many others for which local genetic variation is well described by an underlying, usually probabilistically inferred, haplotype mosaic. Our aim is to provide a framework for coherent estimation of haplotype and diplotype (haplotype pair) effects that takes into account the following: uncertainty in haplotype composition for each individual; uncertainty arising from small sample sizes and infrequently observed haplotype combinations; possible effects of dominance (for noninbred subjects); genetic background; and that provides a means to incorporate data that may be incomplete or has a hierarchical structure. Using the results of a probabilistic haplotype reconstruction as prior information, we obtain posterior distributions at the QTL for both haplotype effects and haplotype composition. Two alternative computational approaches are supplied: a Markov chain Monte Carlo sampler and a procedure based on importance sampling of integrated nested Laplace approximations. Using simulations of QTL in the incipient CC (pre-CC) and Northport HS populations, we compare the accuracy of Diploffect, approximations to it, and more commonly used approaches based on Haley-Knott regression, describing trade-offs between these methods. We also estimate effects for three QTL previously identified in those populations, obtaining posterior intervals that describe how the phenotype might be affected by diplotype substitutions at the modeled locus. | 25,236,455 | [
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Lessons from the contraceptive CHOICE project: the Hull long-acting reversible contraception (LARC) initiative. | To discover whether a hand-out explaining the benefits of intrauterine contraceptives (IUCs) and implants could increase their uptake in Hull, UK. We developed a simple double-sided A4 hand-out. On one side was a script with pictures of copper and levonorgestrel IUCs next to a 20 pence coin and of an implant beside a hairgrip. On the other side was the three-tiered effectiveness chart published in the textbook Contraceptive Technology. We implemented the project in family planning (FP), abortion and antenatal clinics and general practitioner (GP) surgeries. The plan was that the receptionist would give the hand-out to every woman and ask her to read it before seeing a clinician. We evaluated the hand-out in FP clinics and GP practices because routine electronic monitoring reports were available only for these locations. There was no impact in GP practices. There was no overall impact in FP clinics, with the exception of the service hub, in which there was an increase in the proportion of women receiving IUCs or implants of 15.0% between the periods October 2011-April 2012 and May 2012-November 2012 (p=0.0002). This clinic is open 6 days per week and has permanent sexual health staff on the reception desk. The proportion of women receiving IUCs or implants returned to baseline in December 2012-November 2013, when a change in clinic procedure to reduce waiting times caused staff to stop dispensing hand-outs. This was not a formal study, so there was no research coordinator to monitor the project. We think that there was no impact among GPs because the project was not implemented by them. The project was poorly implemented at the four satellite FP clinics. Only the service hub implemented the project, where it had a clear impact. We conclude that when implemented as intended, this simple, very low-cost long-acting reversible contraception intervention was highly effective and also extremely cost effective. | 25,236,471 | [
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S100A8/A9 regulates MMP-2 expression and invasion and migration by carcinoma cells. | Intracellular calprotectin (S100A8/A9) functions in the control of the cell cycle checkpoint at G2/M. Dysregulation of S100A8/A9 appears to cause loss of the checkpoint, which frequently characterizes head and neck squamous cell carcinoma (HNSCC). In the present study, we analyzed carcinoma cells for other S100A8/A9-directed changes in malignant phenotype. Using a S100A8/A9-negative human carcinoma cell line (KB), transfection to express S100A8 and S100A9 caused selective down-regulation of MMP-2 and inhibited in vitro invasion and migration. Conversely, silencing of endogenous S100A8 and S100A9 expression in TR146 cells, a well-differentiated HNSCC cell line, increased MMP-2 activity and in vitro invasion and migration. When MMP-2 expression was silenced, cells appeared to assume a less malignant phenotype. To more closely model the architecture of cell growth in vivo, cells were grown in a 3D collagen substrate, which was compared to 2D. Growth on 3D substrates caused greater MMP-2 expression. Whereas hypermethylation of CpG islands occurs frequently in HNSCC, S100A8/A9-dependent regulation of MMP-2 could not be explained by modification of the upstream promoters of MMP2 or TIMP2. Collectively, these results suggest that intracellular S100A8/A9 contributes to the cancer cell phenotype by modulating MMP-2 expression and activity to regulate cell migration and mobility. | 25,236,491 | [
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MDA-7/IL-24 inhibits Nrf2-mediated antioxidant response through activation of p38 pathway and inhibition of ERK pathway involved in cancer cell apoptosis. | Reactive oxygen species (ROS) have a crucial role in melanoma differentiation-associated gene-7 (MDA-7)/interleukin-24 (IL-24)-induced cancer cell apoptosis. However, cancer cell has a series of protective mechanisms to resist ROS damage. Nuclear factor erythroid 2-related factor 2 (Nrf2) activates antioxidant response element (ARE)-mediated gene expression involved in cellular protection against oxidative stress. As the Nrf2 repressor, Kelch-like ECH-associated protein-1 (Keap1) sequesters Nrf2 in cytoplasm to block Nrf2 nuclear translocation. In the present study, administration of MDA-7/IL-24 by means of tumor-selective replicating adenovirus (ZD55-IL-24) was used to investigate whether ZD55-IL-24 could attenuate Nrf2-mediated oxidative stress response in cancer cell. We found that ZD55-IL-24 effectively strengthened the association between Nrf2 and Keap1 to restrict Nrf2 nuclear translocation, thereby inhibiting ARE-dependent transcriptional response. To evaluate the detailed mechanism underlying the suppression of ZD55-IL-24 on Nrf2-mediated oxidative stress response, we further tested three different mitogen-activated protein kinase (MAPK) signaling pathways in A549 and HeLa cells transfected by ZD55-IL-24. Our data showed that ZD55-IL-24 inhibited extracellular signal-regulated kinase (ERK) signal pathway but activated p38 and c-Jun-NH2-kinase (JNK) signal pathways to exert the tumor-specific apoptosis. Moreover, ERK pathway inhibitor U0126 prevented Nrf2 phosphorylation at Ser40 to retard Nrf2 nuclear translocation, thus decreasing antioxidant gene transcription. In contrast, p38 pathway inhibitor SB203580 obviously promoted the dissociation of Nrf2 from Keap1 to promote antioxidant gene transcription. However, JNK pathway had no effect on Nrf2 subcellular localization or the association of Nrf2 with Keap1. Conclusively, our results indicate that ZD55-IL-24 inhibits Nrf2-mediated oxidative stress response not only by activating p38 signal pathway to potentiate the association of Nrf2 and Keap1 but also by suppressing ERK signal pathway to postpone Nrf2 nuclear translocation. Given the 'dark' side of Nrf2 on carcinoma cell survival and chemoresistance, our study provides a novel explanation about MDA-7/IL-24-induced cancer-specific apoptosis and therapeutic sensitization through suppression of the cytoprotective system. | 25,236,495 | [
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Mutation and Transcriptional Profiling of Formalin-Fixed Paraffin Embedded Specimens as Companion Methods to Immunohistochemistry for Determining Therapeutic Targets in Oropharyngeal Squamous Cell Carcinoma (OPSCC): A Pilot of Proof of Principle. | The role of molecular methods in the diagnosis of head and neck cancer is rapidly evolving and holds great potential for improving outcomes for all patients who suffer from this diverse group of malignancies . However, there is considerable debate as to the best clinical approaches, particularly for Next Generation Sequencing (NGS). The choices of NGS methods such as whole exome, whole genome, whole transcriptomes (RNA-Seq) or multiple gene resequencing panels, each have strengths and weakness based on data quality, the size of the data, the turnaround time for data analysis, and clinical actionability. There have also been a variety of gene expression signatures established from microarray studies that correlate with relapse and response to treatment, but none of these methods have been implemented as standard of care for oropharyngeal squamous cell carcinoma (OPSCC). Because many genomic methodologies are still far from the capabilities of most clinical laboratories, we chose to explore the use of a combination of off the shelf targeted mutation analysis and gene expression analysis methods to complement standard anatomical pathology methods. Specifically, we have used the Ion Torrent AmpliSeq cancer panel in combination with the NanoString nCounter Human Cancer Reference Kit on 8 formalin-fixed paraffin embedded (FFPE) OPSCC tumor specimens, (4) HPV-positive and (4) HPV-negative. Differential expression analysis between HPV-positive and negative groups showed that expression of several genes was highly likely to correlate with HPV status. For example, WNT1, PDGFA and OGG1 were all over-expressed in the positive group. Our results show the utility of these methods with routine FFPE clinical specimens to identify potential therapeutic targets which could be readily applied in a clinical trial setting for clinical laboratories lacking the instrumentation or bioinformatics infrastructure to support comprehensive genomics workflows. To the best of our knowledge, these preliminary experiments are among the earliest to combine both mutational and gene expression profiles using Ion Torrent and NanoString technologies. This reports serves as a proof of principle methodology in OPSCC. | 25,236,499 | [
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Dysregulation of the MIRLET7/HMGA2 axis with methylation of the CDKN2A promoter in myeloproliferative neoplasms. | Overexpression of high mobility group AT-hook 2 (Hmga2), which is negatively regulated by MIRLET7 micro RNAs through 3'-untranslated region (3'UTR), causes proliferative haematopoiesis mimicking myeloproliferative neoplasms (MPNs) and contributes to progression of myelofibrosis in mice. Thus, we investigated HMGA2 mRNA expression in 66 patients with MPNs including 23 polycythaemia vera (PV), 33 essential thrombocythaemia (ET) and 10 primary myelofibrosis (PMF). HMGA2 mRNA expression, especially variant 1 with 3'UTR that contains MIRLET7-specific sites, rather than variant 2 lacking 3'UTR, is frequently deregulated due to decreased MIRLET7 expression in granulocytes from over 20% of PV and ET, and in either granulocytes or CD34(+) cells from 100% of PMF. Patients with deregulated HMGA2 mRNA expression were significantly more likely to show splenomegaly, high serum lactate dehydrogenase values, and methylation of the CDKN2A promoter compared with other patients without deregulation of HMGA2. A histone deacetylase inhibitor, panobinostat, significantly increased MIRLET7 expression and reduced variant 1 of HMGA2 mRNA expression, but not variant 2, in both U937 cells and PMF-derived CD34(+) cells. Moreover, both panobinostat and small interfering RNA of HMGA2 demethylated the CDKN2A promoter in U937 cells. In conclusion, the frequently dysregulated MIRLET7/HMGA2 axis could be a therapeutic target in MPNs. | 25,236,537 | [
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Fe(III) nucleation in the presence of bivalent cations and oxyanions leads to subnanoscale 7 Å polymers. | Highly disordered Fe(III) phases formed in the presence of bivalent cations and oxyanions represent important components of the global Fe cycle due to their potential for rapid turnover and their critical roles in controlling the speciation of major and trace elements. However, a poor understanding of the formation pathway and structure of these Fe phases has prevented assessments of their thermodynamic properties and biogeochemical reactivity. In this work, we derive structural models for the Fe(III)-As(V)-Ca and Fe(III)-P-Ca polymers formed from Fe(II) oxidation and Fe(III) polymerization in the presence of As(V)/P and Ca. The polymer phase consists of a less than 7 Å coherent network of As(V)/P coordinated to Fe(III) polyhedra, with varying amounts of Ca bound directly and indirectly to the oxyanion. This phase forms at the onset of Fe(II) oxidation and, because of its large oxyanion:Fe solids ratio, depletes the oxyanion concentration with only small amounts of Fe. Our results demonstrate that when a steady supply of Fe(III) is provided from an Fe(II) source, these Fe(III) polymers, which dominate oxyanion uptake, form with little dependence on the initial oxyanion concentration. The formation mechanisms and structures of the oxyanion-rich Fe(III) polymers determined in this study enable future thermodynamic investigations of these phases, which are required to model the interrelated biogeochemical cycles of Fe, As(V)/P, and Ca. | 25,236,538 | [
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0.1364156,
0.05972173,
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0.2291506,
-0.1412931... |
Electrocardiographic changes announcing the rapid development of apical hypertrophic cardiomyopathy in an adult male. | We presented the case of an adult male without structural heart disease, who in the period of 3 years developed apical hypertrophic cardiomyopathy. ECG changes preceded the development of ventricular hypertrophy. We discussed the appearance of ventricular enlargement during adulthood, in some cases of hypertrophic cardiomyopathy (HC), and how the ECG abnormalities may precede the onset of ventricular hypertrophy. | 25,236,565 | [
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Nonpharmacotherapeutic Somatic Treatments for Bipolar Disorder (ECT, DBS, rTMS). | Nonpharmacotherapeutic, somatic treatments play an essential role in the management of bipolar disorder (BPD). Studies indicate that electroconvulsive therapy (ECT) is an effective treatment for acute mania, bipolar depression, and mixed affective states. Furthermore, it is an important second-line treatment option, as most pharmacotherapy-resistant patients respond to ECT. Specific challenges for patients with BPD receiving ECT include the risk of mood switching, and the need to evaluate and manage concurrent treatment with lithium and anticonvulsant mood stabilizers. Although the current evidence for alternative and newer physical treatments (e.g., transcranial magnetic stimulation, vagus nerve stimulation, stereotactic ablation, and deep brain stimulation) is preliminary, all of these novel methods show promising potential and merit further research. | 25,236,561 | [
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Evaluation of a quantitative RT-PCR assay to detect HER2 mRNA overexpression for diagnosis and selection of trastuzumab therapy in breast cancer tissue samples. | Breast cancer patients who have a positive result for HER2 overexpression are commonly treated with Herceptin, a HER2-targeted therapy. In the present study, the BrightGen HER2 RT-qDx (Syantra, Calgary, Canada), which is based on a one-tube nested RT-qPCR method that detects HER2 mRNA overexpression, was clinically evaluated in a total of 237 formalin-fixed paraffin-embedded (FFPE) tissue samples from breast cancer patients. Among the 38 HER2 positive samples, which were determined via IHC/FISH methods, 13 samples out of 16 (81.3%) that were IHC2+/FISH+ and 22 samples out of 22 (100%) that were IHC3+ have been decided positive for HER2 expression via the RT-qPCR method. The true positivity and false positivity results for the RT-qPCR were 92% (35/38) and 2% (1/65), respectively. The concordance between RT-qPCR and IHC results and RT-qPCR and IHC/FISH was 87.2% and 92.1%, respectively. Conclusively, the BrightGen HER2 RT-qDx may be a reliable and convenient method that can supplement traditional IHC and FISH methods for efficient use of trastuzumab. | 25,236,569 | [
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... |
Analysis of microRNA expression signatures in malignant pleural mesothelioma, pleural inflammation, and atypical mesothelial hyperplasia reveals common predictive tumorigenesis-related targets. | Pleural chronic inflammation (PP) and mesothelial hyperplasia (HP) may be critical to the development of malignant pleural mesothelioma (MPM). Nonetheless, studies searching for mechanistic links involving microRNA (miRNA) regulation among these interrelated processes have not been reported. Using PCR-Array, we identified the miRNAs expressed in pleural tissues diagnosed with MPM (n=5), PP (n=4) and HP (n=5), as well as in non-cancerous/non-inflammatory tissue as the normal control (n=5). We performed bioinformatics and network analysis of differentially expressed miRNAs to identify tumorigenesis-related miRNAs and their biological networks. The targets of four down-regulated miRNAs in MPM (mir-181a-5p, miR-101-3p, miR-145-5p and miR-212-3p), one in PP (mir-101-3p) and one in HP (mir-494) were significantly enriched in "pathways in cancer". Interactome networks revealed that >50% of down-regulated miRNAs in MPM targeted the signaling-activation molecule MAPK1, the transcription factor ETS1 and the mesenchymal transition-associated molecule FZDA, which have been associated with oncogenic function. Comparative analysis revealed that FZD4 was an overlapping gene target of down-regulated miRNAs that were associated with "pathways in cancer" in MPM, PP and HP. Moreover, MAPK1, ETS1 and Cox-2, a pro-inflammatory enzyme associated with over-expression in cancers, were among the 25 overlapping target genes in MPM and PP. This network analysis revealed a potential combinatory effect of deregulated miRNAs in MPM pathogenesis and indicated potential molecular links between pleural inflammation and hyperplasia with tumorigenesis mechanisms in pleura. | 25,236,577 | [
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In vitro characterization and in vivo behavior of human nucleus pulposus and annulus fibrosus cells in clinical-grade fibrin and collagen-enriched fibrin gels. | The intervertebral disc (IVD) presents a limited self-repair ability and cell-based therapies have been suggested to prevent or treat IVD lesions. Fibrin-based scaffolds as cell carriers are promising candidates in IVD tissue engineering, thanks to their ability to be easily delivered into the defect and to adapt to the lesion shape, to support/retain the injected cells into the implantation site and to favor the production of a suitable extracellular matrix (ECM). We evaluated the in vitro and in vivo behavior of human nucleus pulposus (NP) and annulus fibrosus (AF) cells in a clinical-grade collagen-enriched fibrin that has never been tested before for orthopedic applications, comparing it with clinical-grade fibrin. The survival of IVD cells seeded within fibrin or collagen-enriched fibrin and the ECM synthesis were evaluated by biochemical, immunohistochemical, and transcriptional analyses, prior and after subcutaneous implantation of the gels in nude mice. After 28 days of implantation, NP and AF cells were still detectable within explants, produced tissue-specific ECM, and showed a higher content of glycosaminoglycans (GAGs) and type I and II collagen compared to gels before implantation. Both the fibrin gels, enriched or not with collagen, seemed to be suitable for the culture of AF cells, being able to support the homogeneous synthesis of type I collagen, characteristic of the native fibrocartilaginous AF tissue. Differently, fibrin alone was a more suitable matrix for NP culture, supporting the homogeneous deposition of GAGs and type II collagen. In conclusion, our results suggest to combine AF cells with fibrin, enriched or not with collagen, and NP cells with fibrin alone to maintain the typical features of these cell populations, indicating these clinical-grade materials as viable options in cell-based treatments for IVD lesions. | 25,236,589 | [
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0.00354314... |
Anti-diabetic effects of polysaccharides from Talinum triangulare in streptozotocin (STZ)-induced type 2 diabetic male mice. | The present study evaluated the anti-diabetic effects of the polysaccharides obtained from Talinum triangulare (TTP). Two TTP doses (150 mg/kg and 300 mg/kg · bw/d) were administered orally to normal and streptozotocin (STZ)-induced type 2 diabetic male Kunming mice, respectively. The TTP hypoglycemic and hypolipidemic effects were evaluated by testing the fast blood glucose (FBG) level, fasting serum insulin (FINS), and serum lipids (TC, TG, HDL, LDL) as well as the body, hepar and kidney weights. After four weeks administration, the low-dose group 150 mg/kg · bw/d) and high-dose group (300 mg/kg · bw/d) showed a marked FBG fall rate of 29.85% and 41.18% (FBG fall rate% = ((Diabetic control--TTP group)/Diabetic control) × 100%). The results of FBG and serum lipids indicate that TTP possess significant hypoglycemic effect, but no significant hypolipidemic effect. These results suggest the potential use of TTP as a functional food for the treatment of type 2 diabetic mellitus (T2DM). | 25,236,607 | [
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Cheonggukjang polysaccharides enhance immune activities and prevent cyclophosphamide-induced immunosuppression. | Cheonggukjang is a traditional Korean fermentation product prepared from soybean that is reported to have various biological functions. We previously reported that the polysaccharides from Cheonggukjang (PSCJ) have immunostimulatory activities in RAW 264.7 macrophages and primary cultured splenocytes. In this study, the immunostimulatory activities of the PSCJ were investigated further using various experimental models such as in vitro, ex vivo, and in vivo. The PSCJ was able to stimulate the complement system (ITCH50: 30.6%). In primary cultured mouse peritoneal macrophages, the PSCJ was found to significantly increase nitric oxide and immunostimulatory cytokines (IL-6 and IL-12) production in a concentration-dependent manner (1-100 μg/mL). In the normal mice model, the oral administration of the PSCJ increased the weight of spleen (p < 0.05 at 100 and 200 mg/kg) and improved the phagocytic rates of peritoneal macrophages (p < 0.05 at 200 mg/kg) and lymphocytes proliferation (p < 0.05 at 100 and 200 mg/kg). Similarly, the PSCJ markedly restored the decreased lymphocytes proliferation (p < 0.01 at 200 mg/kg), natural killer cell activity (p < 0.01 at 200mg/kg), and white blood cell count (p<0.01 at 100 and 200 mg/kg) in the cyclophosphamide-induced immunosuppressed mice model. These results suggest that the PSCJ could be utilized as an effective immunostimulatory agent. | 25,236,609 | [
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The cultural environment behind successful maternal death and morbidity reviews. | This paper discusses some of the background principles which, through wide experience of instituting reviews of maternal deaths or near-misses around the world, appear common to their successful introduction. A supportive culture at personal, institutional and national level underpinned by the fostering of professionalism and the development of an ethos of safety against a wider supportive environment is needed. Reviews undertaken at a local level are as beneficial as those at a regional or population level and should be encouraged as a routine part of the quality improvement agenda for each and every healthcare facility. | 25,236,630 | [
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0.03745722,
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0.3058293,
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